Skip to main content
SpringerLink
Log in

The Role of Spliceosome in the Human Breast

  • Chapter
  • First Online:
Role of the Transcriptome in Breast Cancer Prevention

  • 822 Accesses

Abstract

In 1977, work by the Sharp and Roberts labs revealed that genes of higher organisms are “split” or present in several distinct segments along the DNA molecule [1, 2]. The coding regions of the gene are separated by noncoding DNA that is not involved in protein expression. The split gene structure was found when adenoviral mRNAs were hybridized to endonuclease cleavage fragments of single-stranded viral DNA [1]. It was observed that the mRNAs of the mRNA-DNA hybrids contained 5′ and 3′ tails of non-hydrogen bonded regions. When larger fragments of viral DNAs were used, forked structures of looped out DNA were observed when hybridized to the viral mRNAs. It was realized that the looped out regions, the introns, are excised from the precursor mRNAs in a process Sharp named “splicing.” The split gene structure was subsequently found to be common to most eukaryotic genes. Phillip Sharp and Richard J. Roberts were awarded the 1993 Nobel Prize in Physiology or Medicine for their discovery of introns and the splicing process. The advances in this field is unprecedented mainly due to the new implications in our understanding of the basic biological process and its application to the treatment and prevention of many diseases [3, 4]. In this chapter we will describe the main pathways of the splicing mechanism that help the reader to understand the new findings in the human breast and their role in breast cancer prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Berget SM, Moore C, Sharp PA (1977) Spliced segments at 5′ terminus of adenovirus 2 late messenger-RNA. Proc Natl Acad Sci U S A 74:3171–3175

    PubMed  CAS  Google Scholar 

  2. Chow LT, Roberts JM, Lewis JB, Broker TR (1977) A map of cytoplasmic RNA transcripts from lytic adenovirus type 2, determined by electron microscopy of RNA:DNA hybrids. Cell 11:819–836

    PubMed  CAS  Google Scholar 

  3. Query CC (2009) Spliceosome subunit revealed. Nature 458:418–419

    PubMed  CAS  Google Scholar 

  4. Will CL, Lührmann R (2011) Spliceosome structure and function. Cold Spring Harb Perspect Biol 3:a003707

    PubMed  CAS  Google Scholar 

  5. König H, Matter N, Bader R, Thiele W, Müller F (2007) Splicing segregation: the minor spliceosome acts outside the nucleus and controls cell proliferation. Cell 131:718–729

    PubMed  Google Scholar 

  6. Jamison SF, Crow A, Garcia-Blanco MA (1992) The spliceosome assembly pathway in mammalian extracts. Mol Cell Biol 12:4279–4287

    PubMed  CAS  Google Scholar 

  7. Seraphin B, Rosbash M (1989) Identification of functional U1 snRNA pre-messenger RNA complexes committed to spliceosome assembly and splicing. Cell 59:349–358

    PubMed  CAS  Google Scholar 

  8. Legrain P, Seraphin B, Rosbash M (1988) Early commitment of yeast pre-mRNA to the spliceosome pathway. Mol Cell Biol 8:3755–3760

    PubMed  CAS  Google Scholar 

  9. Query CC, Moore MJ, Sharp P (1994) Branch nucleophile selection in pre-mRNA splicing: evidence for the bulged duplex model. Genes Dev 8:587–597

    PubMed  CAS  Google Scholar 

  10. Newby MI, Greenbaum NL (2002) Sculpting of the spliceosomal branch site recognition motif by a conserved pseudouridine. Nat Struct Biol 9:958–965

    PubMed  CAS  Google Scholar 

  11. Burge CB et al (1999) Splicing precursors to mRNAs by the spliceosomes. In: Gesteland RF, Cech TR, Atkins JF (eds) The RNA world. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 525–560

    Google Scholar 

  12. Staley JP, Guthrie C (1998) Mechanical devices of the spliceosome: motors, clocks, springs, and things. Cell 92:315–326

    PubMed  CAS  Google Scholar 

  13. Newman AJ, Teigelkamp S, Beggs JD (1995) snRNA interactions at 5′ and 3′ splice sites monitored by photoactivated crosslinking in yeast spliceosomes. RNA 1:968–980

    PubMed  CAS  Google Scholar 

  14. Chiara MD, Palandjian L, Feld Kramer R, Reed R (1997) Evidence that U5 snRNP recognizes the 3′ splice site for catalytic step II in mammals. EMBO J 16:4746–4759

    PubMed  CAS  Google Scholar 

  15. Moore MJ, Sharp PA (1993) Evidence for two active sites in the spliceosome provided by stereochemistry of pre-mRNA splicing. Nature 365:364–368

    PubMed  CAS  Google Scholar 

  16. Konforti BB, Koziolkiewicz MJ, Konarska MM (1993) Disruption of base pairing between the 5′ splice site and the 5′ end of U1 snRNA is required for spliceosome assembly. Cell 75:863–873

    PubMed  CAS  Google Scholar 

  17. Belitskaya-Levy I, Zeleniuch-Jacquotte A, Russo J, Russo IH, Bordas P, Ahman J, Afanasyeva Y, Johansson R, Lenner P, Li X, de Cicco-Lopez RL, Peri S, Ross E, Russo PA, Santucci-Pereira J, Sheriff FS, Slifker M, Hallmans G, Toniolo P, Arslan AA (2011) Characterization of a genomic signature of pregnancy identified in the breast. Cancer Prev Res 4:1457–1464

    Google Scholar 

  18. Russo J, Santucci-Pereira J, de Cicco RL, Sheriff F, Russo PA, Peri S, Slifker M, Ross E, Mello ML, Vidal BC, Belitskaya-Levy I, Arslan A, Zeleniuch-Jacquotte A, Bordas P, Lenner P, Ahman J, Afanasyeva Y, Hallmans G, Toniolo P, Russo IH (2012) Pregnancy-induced chromatin remodeling in the breast of postmenopausal women. Int J Cancer 131(5):1059–1070

    PubMed  CAS  Google Scholar 

  19. Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080

    PubMed  CAS  Google Scholar 

  20. Gill G (2004) SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? Genes Dev 18:2046–2059

    PubMed  CAS  Google Scholar 

  21. Morgan HD, Santos F, Green K, Dean W, Reik W (2005) Epigenetic reprogramming in mammals. Hum Mol Genet 14:R47–R58

    PubMed  CAS  Google Scholar 

  22. Rottman FM, Bokar JA, Narayan P, Shambaugh ME, Ludwiczak R (1994) N6-adenosine methylation in mRNA: substrate specificity and enzyme complexity. Biochimie 76:1109–1114

    PubMed  CAS  Google Scholar 

  23. Clancy MJ, Shambaugh ME, Timpte CS, Bokar JA (2002) Induction of sporulation in Saccharomyces cerevisiae leads to the formation of N6-methyladenosine in mRNA: a potential mechanism for the activity of the IME4 gene. Nucleic Acids Res 30:4509–4518

    PubMed  CAS  Google Scholar 

  24. Bujnicki JM, Feder M, Radlinska M, Blumenthal RM (2002) Structure prediction and phylogenetic analysis of a functionally diverse family of proteins homologous to the MT-A70 subunit of the human mRNA:m(6)A methyltransferase. J Mol Evol 55:431–444

    PubMed  CAS  Google Scholar 

  25. Sugawara T, Oguro H, Negishi M, Morita Y, Ichikawa H, Iseki T, Yokosuka O, Nakauchi H, Iwama A (2010) FET family proto-oncogene Fus contributes to self-renewal of hematopoietic stem cells. Hematology 38:696–706

    CAS  Google Scholar 

  26. Andersson MK, Ståhlberg A, Arvidsson Y, Olofsson A, Semb H, Stenman G, Nilsson O, Aman P (2008) The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC Cell Biol 9:37

    PubMed  Google Scholar 

  27. Baechtold H, Kuroda M, Sok J, Ron D, Lopez BS, Akhmedov AT (1999) Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation. J Biol Chem 274:34337–34342

    PubMed  CAS  Google Scholar 

  28. Reboll MR, Oumard A, Gazdag AC, Renger I, Ritter B, Schwarzer M, Hauser H, Wood M, Yamada M, Resch K, Nourbakhsh M (2007) NRF IRES activity is mediated by RNA binding protein JKTBP1 and a 14-nt RNA element. RNA 13:1328–1340

    PubMed  CAS  Google Scholar 

  29. Akagi T, Kamei D, Tsuchiya N, Nishina Y, Horiguchi H, Matsui M, Kamma H, Yamada M (2000) Molecular characterization of a mouse heterogeneous nuclear ribonucleoprotein D-like protein JKTBP and its tissue-specific expression. Gene 245:267–273

    PubMed  CAS  Google Scholar 

  30. Taga Y, Miyoshi M, Okajima T, Matsuda T, Nadano D (2010) Identification of heterogeneous nuclear ribonucleoprotein A/B as a cytoplasmic mRNA-binding protein in early involution of the mouse mammary gland. Cell Biochem Funct 28:321–328

    PubMed  CAS  Google Scholar 

  31. Huang PR, Hung SC, Wang TC (2010) Telomeric DNA-binding activities of heterogeneous nuclear ribonucleoprotein A3 in vitro and in vivo. Biochim Biophys Acta 1803:1164–1174

    PubMed  CAS  Google Scholar 

  32. Han SP, Friend LR, Carson JH, Korza G, Barbarese E, Maggipinto M, Hatfield JT, Rothnagel JA, Smith R (2010) Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms. Traffic 11:886–898

    PubMed  CAS  Google Scholar 

  33. Markus MA, Marques FZ, Morris BJ (2011) Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs. PLoS One 6:e28926

    PubMed  Google Scholar 

  34. Harahap IS, Saito T, San LP, Sasaki N, Gunadi, Nurputra DK, Yusoff S, Yamamoto T, Morikawa S, Nishimura N, Lee MJ, Takeshima Y, Matsuo M, Nishio H (2012) Valproic acid increases SMN2 expression and modulates SF2/ASF and hnRNPA1 expression in SMA fibroblast cell lines. Brain Dev 34(3):213–222

    PubMed  Google Scholar 

  35. Flynn RL, Centore RC, O’Sullivan RJ, Rai R, Tse A, Songyang Z, Chang S, Karlseder J, Zou L (2011) TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 471:532–536

    PubMed  CAS  Google Scholar 

  36. Tsuruno C, Ohe K, Kuramitsu M, Kohma T, Takahama Y, Hamaguchi Y, Hamaguchi I, Okuma K (2011) HMGA1a is involved in specific splice site regulation of human immunodeficiency virus type 1. Biochem Biophys Res Commun 406:512–517

    PubMed  CAS  Google Scholar 

  37. Zearfoss NR, Clingman CC, Farley BM, McCoig LM, Ryder SP (2011) SourceQuaking regulates Hnrnpa1 expression through its 3′ UTR in oligodendrocyte precursor cells. PLoS Genet 7:e1001269

    PubMed  Google Scholar 

  38. Zhao L, Mandler MD, Yi H, Feng Y (2010) Quaking I controls a unique cytoplasmic pathway that regulates alternative splicing of myelin-associated glycoprotein. Proc Natl Acad Sci U S A 107:19061–19066

    PubMed  CAS  Google Scholar 

  39. Chen M, Zhang J, Manley JL (2010) Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA. Cancer Res 70:8977–8980

    PubMed  CAS  Google Scholar 

  40. David CJ, Chen M, Assanah M, Canoll P, Manley JL (2010) HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 463:364–368

    PubMed  CAS  Google Scholar 

  41. Gaildrat P, Krieger S, Théry JC, Killian A, Rousselin A, Berthet P, Frébourg T, Hardouin A, Martins A, Tosi M (2010) The BRCA1 c.5434C->G (p.Pro1812Ala) variant induces a deleterious exon 23 skipping by affecting exonic splicing regulatory elements. J Med Genet 47:398–403

    PubMed  CAS  Google Scholar 

  42. Goina E, Skoko N, Pagani F (2008) Binding of DAZAP1 and hnRNPA1/A2 to an exonic splicing silencer in a natural BRCA1 exon 18 mutant. Mol Cell Biol 28:3850–3860

    PubMed  CAS  Google Scholar 

  43. Rosenberger S, De-Castro Arce J, Langbein L, Steenbergen RD, Rösl F (2010) Alternative splicing of human papillomavirus type-16 E6/E6* early mRNA is coupled to EGF signaling via Erk1/2 activation. Proc Natl Acad Sci U S A 107:7006–7011

    PubMed  CAS  Google Scholar 

  44. Yao Z, Duan S, Hou D, Wang W, Wang G, Liu Y, Wen L, Wu M (2010) B23 acts as a nucleolar stress sensor and promotes cell survival through its dynamic interaction with hnRNPU and hnRNPA1. Oncogene 29:1821–1834

    PubMed  CAS  Google Scholar 

  45. Orvain C, Matre V, Gabrielsen OS (2008) The transcription factor c-Myb affects pre-mRNA splicing. Biochem Biophys Res Commun 372:309–313

    PubMed  CAS  Google Scholar 

  46. Donev R, Newall A, Thome J, Sheer D (2007) A role for SC35 and hnRNPA1 in the determination of amyloid precursor protein isoforms. Mol Psychiatry 12:681–690

    PubMed  CAS  Google Scholar 

  47. Christian K, Lang M, Maurel P, Raffalli-Mathieu F (2004) Interaction of heterogeneous nuclear ribonucleoprotein A1 with cytochrome P450 2A6 mRNA: implications for post-transcriptional regulation of the CYP2A6 gene. Mol Pharmacol 65:1405–1414

    PubMed  CAS  Google Scholar 

  48. Chen H, Hewison M, Hu B, Adams JS (2003) Heterogeneous nuclear ribonucleoprotein (hnRNP) binding to hormone response elements: a cause of vitamin D resistance. Proc Natl Acad Sci U S A 100:6109–6114

    PubMed  CAS  Google Scholar 

  49. He Y, Brown MA, Rothnagel JA, Saunders NA, Smith R (2005) Roles of heterogeneous nuclear ribonucleoproteins A and B in cell proliferation. J Cell Sci 118:3173–3183

    PubMed  CAS  Google Scholar 

  50. Yan-Sanders Y, Hammons GJ, Lyn-Cook BD (2002) Increased expression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP) in pancreatic tissue from smokers and pancreatic tumor cells. Cancer Lett 183:215–220

    PubMed  CAS  Google Scholar 

  51. Tockman MS, Mulshine JL, Piantadosi S, Erozan YS, Gupta PK, Ruckdeschel JC, Taylor PR, Zhukov T, Zhou WH, Qiao YL, Yao SX (1997) Prospective detection of preclinical lung cancer: results from two studies of heterogeneous nuclear ribonucleoprotein A2/B1 overexpression. Clin Cancer Res 3:2237–2246

    PubMed  CAS  Google Scholar 

  52. Golan-Gerstl R, Cohen M, Shilo A, Suh SS, Bakàcs A, Coppola L, Karni R (2011) Splicing factor hnRNP A2/B1 regulates tumor suppressor gene splicing and is an oncogenic driver in glioblastoma. Cancer Res 71:4464–4472

    PubMed  CAS  Google Scholar 

  53. Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB (1993) bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74:597–608

    PubMed  CAS  Google Scholar 

  54. Olopade OI, Adeyanju MO, Safa AR, Hagos F, Mick R, Thompson CB, Recant WM (1997) Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases. Cancer J Sci Am 3:230–237

    PubMed  CAS  Google Scholar 

  55. Chen ZY, Cai L, Zhu J, Chen M, Chen J, Li ZH, Liu XD, Wang SG, Bie P, Jiang P, Dong JH, Li XW (2011) Fyn requires HnRNPA2B1 and Sam68 to synergistically regulate apoptosis in pancreatic cancer. Carcinogenesis 32:1419–1426

    PubMed  CAS  Google Scholar 

  56. Fang X, Yoon JG, Li L, Tsai YS, Zheng S, Hood L, Goodlett DR, Foltz G, Lin B (2011) Landscape of the SOX2 protein-protein interactome. Proteomics 11:921–934

    PubMed  CAS  Google Scholar 

  57. Santarosa M, Del Col L, Viel A, Bivi N, D’Ambrosio C, Scaloni A, Tell G, Maestro R (2010) BRCA1 modulates the expression of hnRNPA2B1 and KHSRP. Cell Cycle 9:4666–4673

    PubMed  CAS  Google Scholar 

  58. Elliott DJ, Venables JP, Newton CS, Lawson D, Boyle S, Eperon IC, Cooke HJ (2000) An evolutionarily conserved germ cell-specific hnRNP is encoded by a retrotransposed gene. Hum Mol Genet 9:2117–2124

    Google Scholar 

  59. Dempsey LA, Li MJ, DePace A, Bray-Ward P, Maizels N (1998) The human HNRPD locus maps to 4q21 and encodes a highly conserved protein. Genomics 49:378–384

    PubMed  CAS  Google Scholar 

  60. Ing NH (2010) Estradiol up-regulates expression of the A  +  U-rich binding factor 1 (AUF1) gene in the sheep uterus. J Steroid Biochem Mol Biol 122:172–179

    PubMed  CAS  Google Scholar 

  61. Boopathi E, Lenka N, Prabu SK, Fang JK, Wilkinson F, Atchison M, Giallongo A, Avadhani NG (2004) Regulation of murine cytochrome c oxidase Vb gene expression during myogenesis: YY-1 and heterogeneous nuclear ribonucleoprotein D-like protein (JKTBP1) reciprocally regulate transcription activity by physical interaction with the BERF-1/ZBP-89 factor. J Biol Chem 279:35242–35254

    PubMed  CAS  Google Scholar 

  62. Tsuchiya N, Kamei D, Takano A, Matsui T, Yamada M (1998) Cloning and characterization of a cDNA encoding a novel heterogeneous nuclear ribonucleoprotein-like protein and its expression in myeloid leukemia cells. J Biochem 123:499–507

    PubMed  CAS  Google Scholar 

  63. Bandiera A, Tell G, Marsich E, Scaloni A, Pocsfalvi G, Akintunde Akindahunsi A, Cesaratto L, Manzini G (2003) Cytosine-block telomeric type DNA-binding activity of hnRNP proteins from human cell lines. Arch Biochem Biophys 409:305–314

    PubMed  CAS  Google Scholar 

  64. Kamei D, Tsuchiya N, Yamazaki M, Meguro H, Yamada M (1999) Two forms of expression and genomic structure of the human heterogeneous nuclear ribonucleoprotein D-like JKTBP gene (HNRPDL). Gene 228:13–22

    PubMed  CAS  Google Scholar 

  65. Kotlajich MV, Hertel KJ (2008) Death by splicing: tumor suppressor RBM5 freezes splice-site pairing. Mol Cell 32:162–164

    PubMed  CAS  Google Scholar 

  66. Fushimi K, Ray P, Kar A, Wang L, Sutherland LC, Wu JY (2008) Up-regulation of the proapoptotic caspase 2 splicing isoform by a candidate tumor suppressor, RBM5. Proc Natl Acad Sci U S A 105:15708–15713

    PubMed  CAS  Google Scholar 

  67. Sutherland LC, Wang K, Robinson AG (2010) RBM5 as a putative tumor suppressor gene for lung cancer. J Thorac Oncol 5:294–298

    PubMed  Google Scholar 

  68. Rintala-Maki ND, Sutherland LC (2009) Identification and characterisation of a novel antisense non-coding RNA from the RBM5 gene locus. Gene 445:7–16

    PubMed  CAS  Google Scholar 

  69. Shu Y, Rintala-Maki ND, Wall VE, Wang K, Goard CA, Langdon CE, Sutherland LC (2007) The apoptosis modulator and tumour suppressor protein RBM5 is a phosphoprotein. Cell Biochem Funct 25:643–653

    PubMed  CAS  Google Scholar 

  70. Kobayashi T, Ishida J, Musashi M, Ota S, Yoshida T, Shimizu Y, Chuma M, Kawakami H, Asaka M, Tanaka J, Imamura M, Kobayashi M, Itoh H, Edamatsu H, Sutherland LC, Brachmann RK (2011) p53 transactivation is involved in the antiproliferative activity of the putative tumor suppressor RBM5. Int J Cancer 128:304–318

    PubMed  CAS  Google Scholar 

  71. Farina B, Fattorusso R, Pellecchia M (2011) Targeting zinc finger domains with small molecules: solution structure and binding studies of the RanBP2-type zinc finger of RBM5. Chembiochem 12:2837–2845

    PubMed  CAS  Google Scholar 

  72. Nguyen CD, Mansfield RE, Leung W, Vaz PM, Loughlin FE, Grant RP, Mackay JP (2011) Characterization of a family of RanBP2-type zinc fingers that can recognize single-stranded RNA. J Mol Biol 407:273–283

    PubMed  CAS  Google Scholar 

  73. Oh JJ, Boctor BN, Jimenez CA, Lopez R, Koegel AK, Taschereau EO, Phan DT, Jacobsen SE, Slamon DJ (2008) Promoter methylation study of the H37/RBM5 tumor suppressor gene from the 3p21.3 human lung cancer tumor suppressor locus. Hum Genet 123:55–64

    PubMed  CAS  Google Scholar 

  74. Wang K, Ubriaco G, Sutherland LC (2007) RBM6-RBM5 transcription-induced chimeras are differentially expressed in tumours. BMC Genomics 8:348

    PubMed  Google Scholar 

  75. Oh JJ, Koegel AK, Phan DT, Razfar A, Slamon DJ (2007) The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers. Lung Cancer 58:7–14

    PubMed  Google Scholar 

  76. Rintala-Maki ND, Goard CA, Langdon CE, Wall VE, Traulsen KE, Morin CD, Bonin M, Sutherland LC (2007) Expression of RBM5-related factors in primary breast tissue. J Cell Biochem 100:1440–1458

    PubMed  CAS  Google Scholar 

  77. Sillekens PT, Beijer RP, Habets WJ, van Verooij WJ (1989) Molecular cloning of the cDNA for the human U2 snRNA-specific A′ protein. Nucleic Acids Res 17:1893–1906

    PubMed  CAS  Google Scholar 

  78. Entrez gene: SNRPA1 small nuclear ribonucleoprotein polypeptide A′. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6627

    Google Scholar 

  79. Yamamoto ML, Clark TA, Gee SL, Kang JA, Schweitzer AC, Wickrema A, Conboy JG (2009) Alternative pre-mRNA splicing switches modulate gene expression in late erythropoiesis. Blood 113:3363–3370

    PubMed  CAS  Google Scholar 

  80. Spritz RA, Strunk K, Surowy CS, Hoch SO, Barton DE, Francke U (1987) The human U1-70K snRNP protein: cDNA cloning, chromosomal localization, expression, alternative splicing and RNA-binding. Nucleic Acids Res 15:10373–10391

    PubMed  CAS  Google Scholar 

  81. Gridley DS, Coutrakon GB, Rizvi A, Bayeta EJ, Luo-Owen X, Makinde AY, Baqai F, Koss P, Slater JM, Pecaut MJ (2008) Low-dose photons modify liver response to simulated solar particle event protons. Radiat Res 169:280–287

    PubMed  CAS  Google Scholar 

  82. Xu GM, Arnaout MA (2002) WAC, a novel WW domain-containing adapter with a coiled-coil region, is colocalized with splicing factor SC35. Genomics 79:87–94

    PubMed  CAS  Google Scholar 

  83. Sleeman JE, Ajuh P, Lamond AI (2001) snRNP protein expression enhances the formation of Cajal bodies containing p80-coilin and SMN. J Cell Sci 114(pt 24):4407–4419

    PubMed  CAS  Google Scholar 

  84. Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G (2002) Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins. J Biol Chem 277:5631–5636

    PubMed  CAS  Google Scholar 

  85. Kaufman KM, Kirby MY, McClain MT, Harley JB, James JA (2001) Lupus autoantibodies recognize the product of an alternative open reading frame of SmB/B′. Biochem Biophys Res Commun 285:1206–1212

    PubMed  CAS  Google Scholar 

  86. Saltzman AL, Pan Q, Blencowe BJ (2011) Regulation of alternative splicing by the core spliceosomal machinery. Genes Dev 25:373–384

    PubMed  Google Scholar 

  87. Wang X, Pankratz VS, Fredericksen Z, Tarrell R, Karaus M, McGuffog L, Pharaoh PD, Ponder BA, Dunning AM, Peock S, Cook M, Oliver C, Frost D et al (2010) Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers. Hum Mol Genet 19:2886–2897

    PubMed  CAS  Google Scholar 

  88. Toyota CG, Davis MD, Cosman AM, Hebert MD (2010) Coilin phosphorylation mediates interaction with SMN and SmB′. Chromosoma 119:205–215

    PubMed  CAS  Google Scholar 

  89. Velma V, Carrero ZI, Cosman AM, Hebert MD (2010) Coilin interacts with Ku proteins and inhibits in vitro non-homologous DNA end joining. FEBS Lett 584:4735–4759

    PubMed  CAS  Google Scholar 

  90. Yi Y, Nandana S, Case T, Nelson C, Radmilovic T, Matusik RJ, Tsuchiya KD (2009) Candidate metastasis suppressor genes uncovered by array comparative genomic hybridization in a mouse allograft model of prostate cancer. Mol Cytogenet 2:18

    PubMed  Google Scholar 

  91. Rapkins RW, Hore T, Smithwick M, Ager E, Pask AJ, Renfree MB, Kohn M, Hameister H, Nicholls RD, Deakin JE, Graves JA (2006) Recent assembly of an imprinted domain from non-imprinted components. PLoS Genet 2:e182

    PubMed  Google Scholar 

  92. Deshmukh US, Kannapell CC, Fu SM (2002) Immune responses to small nuclear ribonucleoproteins: antigen-dependent distinct B cell epitope spreading patterns in mice immunized with recombinant polypeptides of small nuclear ribonucleoproteins. J Immunol 168(10):5326–5332

    PubMed  CAS  Google Scholar 

  93. Patnaik MM, Lasho TL, Hodnefield JM, Knudson RA, Ketterling RP, Garcia-Manero G, Steensma DP, Pardanani A, Hanson CA, Tefferi A (2012) SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value. Blood 119:569–572

    PubMed  CAS  Google Scholar 

  94. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, Shih LY, Haferlach T, Chiba S, Nakauchi H, Miyano S, Ogawa S (2011) Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 478:64–69

    PubMed  CAS  Google Scholar 

  95. Quesada V, Conde L, Villamor N, Ordóñez GR, Jares P, Bassaganyas L, Ramsay AJ, Beà S, Pinyol M, Martínez-Trillos A, López-Guerra M, Colomer D, Navarro A, Baumann T, Aymerich M, Rozman M, Delgado J, Giné E, Hernández JM, González-Díaz M, Puente DA, Velasco G, Freije JM, Tubío JM, Royo R, Gelpí JL, Orozco M, Pisano DG, Zamora J, Vázquez M, Valencia A, Himmelbauer H, Bayés M, Heath S, Gut M, Gut I, Estivill X, López-Guillermo A, Puente XS, Campo E, López-Otín C (2011) Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 44:47–52

    PubMed  Google Scholar 

  96. Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, Werner L, Sivachenko A, DeLuca DS, Zhang L, Zhang W, Vartanov AR, Fernandes SM, Goldstein NR, Folco EG, Cibulskis K, Tesar B, Sievers QL, Shefler E, Gabriel S, Hacohen N, Reed R, Meyerson M, Golub TR, Lander ES, Neuberg D, Brown JR, Getz G, Wu CJ (2011) SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 365:2497–2506

    PubMed  CAS  Google Scholar 

  97. Rossi D, Bruscaggin A, Spina V, Rasi S, Khiabanian H, Messina M, Fangazio M, Vaisitti T, Monti S, Chiaretti S, Guarini A, Del Giudice I, Cerri M, Cresta S, Deambrogi C, Gargiulo E, Gattei V, Forconi F, Bertoni F, Deaglio S, Rabadan R, Pasqualucci L, Foà R, Dalla-Favera R, Gaidano G (2011) Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood 118:6904–6908

    PubMed  CAS  Google Scholar 

  98. Bermingham JR Jr, Arden KC, Naumova AK, Sapienza C, Viars CS, Fu XD, Khotz J, Manley JL, Rosenfeld MG (1996) Chromosomal localization of mouse and human genes encoding the splicing factors ASF/SF2 (SFRS1) and SC-35 (SFRS2). Genomics 29:70–79

    Google Scholar 

  99. Fu XD, Maniatis T (1992) Isolation of a complementary DNA that encodes the mammalian splicing factor SC35. Science 256:535–538

    PubMed  CAS  Google Scholar 

  100. Bogolyubova IO (2011) Transcriptional activity of nuclei in 2-cell blocked mouse embryos. Tissue Cell 43:262–265

    PubMed  CAS  Google Scholar 

  101. Clayton JC, Phelan M, Goult BT, Hautbergue GM, Wilson SA, Lian LY (2011) The 1H, 13C and 15N backbone and side-chain assignment of the RRM domain of SC35, a regulator of pre-mRNA splicing. Biomol NMR Assign 5:7–10

    PubMed  CAS  Google Scholar 

  102. Xiao R, Sun Y, Ding JH, Lin S, Rose DW, Rosenfeld MG, Fu XD, Li X (2007) Splicing regulator SC35 is essential for genomic stability and cell proliferation during mammalian organogenesis. Mol Cell Biol 27:5393–5402

    PubMed  CAS  Google Scholar 

  103. Lin S, Coutinho-Mansfield G, Wang D, Pandit S, Fu XD (2008) The splicing factor SC35 has an active role in transcriptional elongation. Nat Struct Mol Biol 15:819–826

    PubMed  CAS  Google Scholar 

  104. Yang L, Li N, Wang C, Yu Y, Yuan L, Zhang M, Cao X (2004) Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma cells. J Biol Chem 279:11639–11648

    PubMed  CAS  Google Scholar 

  105. van Abel D, Hölzel DR, Jain S, Lun FM, Zheng YW, Chen EZ, Sun H, Chiu RW, Lo YM, van Dijk M, Oudejans CB (2011) SFRS7-mediated splicing of tau exon 10 is directly regulated by STOX1A in glial cells. PLoS One 6:e21994

    PubMed  Google Scholar 

  106. Escudero-Paunetto L, Li L, Hernandez FP, Sandri-Goldin RM (2010) SR proteins SRp20 and 9G8 contribute to efficient export of herpes simplex virus 1 mRNAs. Virology 401:155–164

    PubMed  CAS  Google Scholar 

  107. Valente ST, Gilmartin GM, Venkatarama K, Arriagada G, Goff SP (2009) HIV-1 mRNA 3′ end processing is distinctively regulated by eIF3f, CDK11, and splice factor 9G8. Mol Cell 36:279–289

    PubMed  CAS  Google Scholar 

  108. Swartz JE, Bor YC, Misawa Y, Rekosh D, Hammarskjold ML (2007) The shuttling SR protein 9G8 plays a role in translation of unspliced mRNA containing a constitutive transport element. J Biol Chem 282:19844–19853

    PubMed  CAS  Google Scholar 

  109. Brasch-Andersen C, Tan Q, Børglum AD, Haagerup A, Larsen TR, Vestbo J, Kruse TA (2006) Significant linkage to chromosome 12q24.32-q24.33 and identification of SFRS8 as a possible asthma susceptibility gene. Thorax 61:874–879

    PubMed  CAS  Google Scholar 

  110. Sampson ND, Hewitt JE (2003) SF4 and SFRS14, two related putative splicing factors on human chromosome 19p13.11. Gene 305:91–100

    PubMed  CAS  Google Scholar 

  111. Entrez gene: SFRS14 splicing factor, arginine/serine-rich 14. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10147

    Google Scholar 

  112. Katsu R, Onogi H, Wada K, Kawaguchi Y, Hagiwara M (2002) Novel SR-rich-related protein clasp specifically interacts with inactivated Clk4 and induces the exon EB inclusion of Clk. J Biol Chem 277:44220–44228

    PubMed  CAS  Google Scholar 

  113. Entrez gene: SFRS16 splicing factor, arginine/serine-rich 16. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=11129

    Google Scholar 

  114. Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (1998) Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res 5:31–39

    PubMed  CAS  Google Scholar 

  115. Kojima T, Zama T, Wada K, Onogi H, Hagiwara M (2001) Cloning of human PRP4 reveals interaction with Clk1. J Biol Chem 276:32247–32256

    PubMed  CAS  Google Scholar 

  116. Huang Y, Deng T, Winston BW (2000) Characterization of hPRP4 kinase activation: potential role in signaling. Biochem Biophys Res Commun 271:456–463

    PubMed  CAS  Google Scholar 

  117. Entrez gene: PRPF4B PRP4 pre-mRNA processing factor 4 homolog B (yeast). http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8899

    Google Scholar 

  118. Dellaire G, Makarov EM, Cowger JJ, Longman D, Sutherland HG, Lührmann R, Torchia J, Bickmore WA (2002) Mammalian PRP4 kinase copurifies and interacts with components of both the U5 snRNP and the N-CoR deacetylase complexes. Mol Cell Biol 22:5141–5156

    PubMed  CAS  Google Scholar 

  119. Tonevitsky EA, Trushkin EV, Shkurnikov MU, Akimov EB, Sakharov DA (2009) Changed profile of splicing regulator genes expression in response to exercise. Bull Exp Biol Med 147:733–736

    PubMed  CAS  Google Scholar 

  120. Huang B, Ahn YT, McPherson L, Clayberger C, Krensky AM (2007) Interaction of PRP4 with Kruppel-like factor 13 regulates CCL5 transcription. J Immunol 178:7081–7087

    PubMed  CAS  Google Scholar 

  121. Bennett EM, Lever AM, Allen JF (2004) Human immunodeficiency virus type 2 Gag interacts specifically with PRP4, a serine-threonine kinase, and inhibits phosphorylation of splicing factor SF2. J Virol 78:11303–11312

    PubMed  CAS  Google Scholar 

  122. Hurschler BA, Harris DT, Grosshans H (2011) The type II poly(A)-binding protein PABP-2 genetically interacts with the let-7 miRNA and elicits heterochronic phenotypes in Caenorhabditis elegans. Nucleic Acids Res 39:5647–5657

    PubMed  CAS  Google Scholar 

  123. Lemay JF, D’Amours A, Lemieux C, Lackner DH, St-Sauveur VG, Bähler J, Bachand F (2010) The nuclear poly(A)-binding protein interacts with the exosome to promote synthesis of noncoding small nucleolar RNAs. Mol Cell 37:34–45

    PubMed  CAS  Google Scholar 

  124. Kühn U, Gündel M, Knoth A, Kerwitz Y, Rüdel S, Wahle E (2009) Poly(A) tail length is controlled by the nuclear poly(A)-binding protein regulating the interaction between poly(A) polymerase and the cleavage and polyadenylation specificity factor. J Biol Chem 284:22803–22814

    PubMed  Google Scholar 

  125. Lemay JF, Lemieux C, St-André O, Bachand F (2010) Crossing the borders: poly(A)-binding proteins working on both sides of the fence. RNA Biol 7:291–295

    PubMed  CAS  Google Scholar 

  126. Raz V, Abraham T, van Zwet EW, Dirks RW, Tanke HJ, van der Maarel SM (2011) Reversible aggregation of PABPN1 pre-inclusion structures. Nucleus 2:208–218

    PubMed  Google Scholar 

  127. Raz V, Routledge S, Venema A, Buijze H, van der Wal E, Anvar S, Straasheijm KR, Klooster R, Antoniou M, van der Maarel SM (2011) Modeling oculopharyngeal muscular dystrophy in myotube cultures reveals reduced accumulation of soluble mutant PABPN1 protein. Am J Pathol 179:1988–2000

    PubMed  CAS  Google Scholar 

  128. Davies JE, Rubinsztein DC (2011) Over-expression of BCL2 rescues muscle weakness in a mouse model of oculopharyngeal muscular dystrophy. Hum Mol Genet 20:1154–1163

    PubMed  CAS  Google Scholar 

  129. Pasco MY, Rotili D, Altucci L, Farina F, Rouleau GA, Mai A, Neri C (2010) Characterization of sirtuin inhibitors in nematodes expressing a muscular dystrophy protein reveals muscle cell and behavioral protection by specific sirtinol analogues. J Med Chem 53:1407–1411

    PubMed  CAS  Google Scholar 

  130. Takagaki Y, Manley JL (1994) A polyadenylation factor subunit is the human homologue of the Drosophila suppressor of forked protein. Nature 372:471–474

    PubMed  CAS  Google Scholar 

  131. Entrez gene: CSTF3 cleavage stimulation factor, 3′ pre-RNA, subunit 3, 77kDa. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1479

    Google Scholar 

  132. Takagaki Y, Manley JL (2000) Complex protein interactions within the human polyadenylation machinery identify a novel component. Mol Cell Biol 20:1515–1525

    PubMed  CAS  Google Scholar 

  133. Park JS, Young Yoon S, Kim JM, Yeom YI, Kim YS, Kim NS (2004) Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray. Cancer Lett 214:19–33

    PubMed  CAS  Google Scholar 

  134. Yoon DW, Lee H, Seol W, DeMaria M, Rosenzweig M, Jung JU (1997) Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation. Immunity 6:571–582

    PubMed  CAS  Google Scholar 

  135. Gruter P, Tabernero C, von Kobbe C, Schmitt C, Saavedra C, Bachi A, Wilm M, Felber BK, Izaurralde E (1998) TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol Cell 1:649–659

    PubMed  CAS  Google Scholar 

  136. Atsapkina AA, Golubkova EV, Kasatkina VV, Avanesian EO, Ivankova NA, Mamon LA (2010) Spermatogenesis in Drosophila melanogaster: the role of the basic transport receptor of the mRNA (Dm NXF1). Tsitologiia 52:574–579

    PubMed  CAS  Google Scholar 

  137. Katahira J, Strässer K, Podtelejnikov A, Mann M, Jung JU, Hurt E (1999) The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human. EMBO J 18:2593–2609

    PubMed  CAS  Google Scholar 

  138. Teplova M, Wohlbold L, Khin NW, Izaurralde E, Patel DJ (2011) Structure-function studies of nucleocytoplasmic transport of retroviral genomic RNA by mRNA export factor TAP. Nat Struct Mol Biol 18:990–998

    PubMed  CAS  Google Scholar 

  139. Coyle JH, Bor YC, Rekosh D, Hammarskjold ML (2011) The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. RNA 17:1344–1356

    PubMed  CAS  Google Scholar 

  140. Hernandez FP, Sandri-Goldin RM (2010) Head-to-tail intramolecular interaction of herpes simplex virus type 1 regulatory protein ICP27 is important for its interaction with cellular mRNA export receptor TAP/NXF1. MBio 1(5):e00268–10

    PubMed  CAS  Google Scholar 

  141. Floyd JA, Gold DA, Concepcion D, Poon TH, Wang X, Keithley E, Chen D, Ward EJ, Chinn SB, Friedman RA, Yu HT, Moriwaki K, Shiroishi T, Hamilton BA (2003) A natural allele of Nxf1 suppresses retrovirus insertional mutations. Nat Genet 35:221–228

    PubMed  CAS  Google Scholar 

  142. Markovtsov V, Nikolic JM, Goldman JA, Turck CW, Chou MY, Black DL (2000) Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein. Mol Cell Biol 20:7463–7479

    PubMed  CAS  Google Scholar 

  143. Entrez gene: PTBP2 polypyrimidine tract binding protein 2. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=58155

    Google Scholar 

  144. Tang ZZ, Sharma S, Zheng S, Chawla G, Nikolic J, Black DL (2011) Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium channel transcript by polypyrimidine tract-binding protein. J Biol Chem 286:10007–10016

    PubMed  CAS  Google Scholar 

  145. Nowak U, Matthews AJ, Zheng S, Chaudhuri J (2011) The splicing regulator PTBP2 interacts with the cytidine deaminase AID and promotes binding of AID to switch-region DNA. Nat Immunol 12:160–166

    PubMed  CAS  Google Scholar 

  146. Bitel CL, Perrone-Bizzozero NI, Frederikse PH (2010) HuB/C/D, nPTB, REST4, and miR-124 regulators of neuronal cell identity are also utilized in the lens. Mol Vis 16:2301–2316

    PubMed  CAS  Google Scholar 

  147. Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G, Ostrow K, Shiue L, Ares M Jr, Black DL (2007) A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev 21:1636–1652

    PubMed  CAS  Google Scholar 

  148. Lu X, Timchenko NA, Timchenko LT (1999) Cardiac elav-type RNA-binding protein (ETR-3) binds to RNA CUG repeats expanded in myotonic dystrophy. Hum Mol Genet 8:53–60

    PubMed  CAS  Google Scholar 

  149. Entrez gene: CUGBP2 CUG triplet repeat, RNA binding protein 2. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10659

    Google Scholar 

  150. Anant S, Henderson JO, Mukhopadhyay D, Navaratnam N, Kennedy S, Min J, Davidson NO (2001) Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. CUGBP2 modulates C to U editing of apolipoprotein B mRNA by interacting with apobec-1 and ACF, the apobec-1 complementation factor. J Biol Chem 276:47338–47351

    PubMed  CAS  Google Scholar 

  151. Dembowski JA, Grabowski PJ (2009) The CUGBP2 splicing factor regulates an ensemble of branchpoints from perimeter binding sites with implications for autoregulation. PLoS Genet 5:e1000595

    PubMed  Google Scholar 

  152. Subramaniam D, Natarajan G, Ramalingam S, Ramachandran I, May R, Queimado L, Houchen CW, Anant S (2008) Translation inhibition during cell cycle arrest and apoptosis: Mcl-1 is a novel target for RNA binding protein CUGBP2. Am J Physiol Gastrointest Liver Physiol 294:G1025–G1032

    PubMed  CAS  Google Scholar 

  153. Ramalingam S, Natarajan G, Schafer C, Subramaniam D, May R, Ramachandran I, Queimado L, Houchen CW, Anant S (2008) Novel intestinal splice variants of RNA-binding protein CUGBP2: isoform-specific effects on mitotic catastrophe. Am J Physiol Gastrointest Liver Physiol 294:G971–G9781

    PubMed  CAS  Google Scholar 

  154. Fuller-Pace FV, Moore HC (2011) RNA helicases p68 and p72: multifunctional proteins with important implications for cancer development. Future Oncol 7:239–251

    PubMed  CAS  Google Scholar 

  155. Mooney SM, Grande JP, Salisbury JL, Janknecht R (2010) Sumoylation of p68 and p72 RNA helicases affects protein stability and transactivation potential. Biochemistry 49(1):1–10

    PubMed  CAS  Google Scholar 

  156. Janknecht R (2010) Multi-talented DEAD-box proteins and potential tumor promoters: p68 RNA helicase (DDX5) and its paralog, p72 RNA helicase (DDX17). Am J Transl Res 2:223–234

    PubMed  CAS  Google Scholar 

  157. Dutertre M, Gratadou L, Dardenne E, Germann S, Samaan S, Lidereau R, Driouch K, de la Grange P, Auboeuf D (2010) Estrogen regulation and physiopathologic significance of alternative promoters in breast cancer. Cancer Res 70:3760–3770

    PubMed  CAS  Google Scholar 

  158. Fuller-Pace FV, Ali S (2008) The DEAD box RNA helicases p68 (Ddx5) and p72 (Ddx17): novel transcriptional co-regulators. Biochem Soc Trans 36:609–612

    PubMed  CAS  Google Scholar 

  159. Mooney SM, Goel A, D’Assoro AB, Salisbury JL, Janknecht R (2010) Pleiotropic effects of p300-mediated acetylation on p68 and p72 RNA helicase. J Biol Chem 285:30443–30452

    PubMed  CAS  Google Scholar 

  160. Paul S, Dansithong W, Jog SP, Holt I, Mittal S, Brook JD, Morris GE, Comai L, Reddy S (2011) Expanded CUG repeats dysregulate RNA splicing by altering the stoichiometry of the muscleblind 1 complex. J Biol Chem 286:38427–38438

    PubMed  CAS  Google Scholar 

  161. Gao G, Xie A, Huang SC, Zhou A, Zhang J, Herman AM, Ghassemzadeh S, Jeong EM, Kasturirangan S, Raicu M, Sobieski MA II, Bhat G, Tatooles A, Benz EJ Jr, Kamp TJ, Dudley SC Jr (2011) Role of RBM25/LUC7L3 in abnormal cardiac sodium channel splicing regulation in human heart failure. Circulation 124:1124–1131

    PubMed  CAS  Google Scholar 

  162. Alpatov R, Munguba GC, Caton P, Joo JH, Shi Y, Shi Y, Hunt ME, Sugrue SP (2004) Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene. Mol Cell Biol 24:10223–10235

    PubMed  CAS  Google Scholar 

  163. Jeronimo C, Forget D, Bouchard A, Li Q, Chua G, Poitras C, Thérien C, Bergeron D, Bourassa S, Greenblatt J, Chabot B, Poirier GG, Hughes TR, Blanchette M, Price DH, Coulombe B (2007) Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Mol Cell 27:262–274

    PubMed  CAS  Google Scholar 

  164. Alpatov R, Shi Y, Munguba GC, Moghimi B, Joo JH, Bungert J, Sugrue SP (2008) Corepressor CtBP and nuclear speckle protein Pnn/DRS differentially modulate transcription and splicing of the E-cadherin gene. Mol Cell Biol 28:1584–1595

    PubMed  CAS  Google Scholar 

  165. Joo JH, Taxter TJ, Munguba GC, Kim YH, Dhaduvai K, Dunn NW, Degan WJ, Oh SP, Sugrue SP (2010) Pinin modulates expression of an intestinal homeobox gene, Cdx2, and plays an essential role for small intestinal morphogenesis. Dev Biol 345:191–203

    PubMed  CAS  Google Scholar 

  166. Hsu SY, Chen YJ, Ouyang P (2011) Pnn and SR family proteins are differentially expressed in mouse central nervous system. Histochem Cell Biol 135:361–373

    PubMed  CAS  Google Scholar 

  167. Chiu Y, Ouyang P (2006) Loss of Pnn expression attenuates expression levels of SR family splicing factors and modulates alternative pre-mRNA splicing in vivo. Biochem Biophys Res Commun 341:663–671

    PubMed  CAS  Google Scholar 

  168. Leu S, Ouyang P (2006) Spatial and temporal expression profile of pinin during mouse development. Gene Expr Patterns 6:620–631

    PubMed  CAS  Google Scholar 

  169. Gonzalez-Santos JM, Wang A, Jones J, Ushida C, Liu J, Hu J (2002) Central region of the human splicing factor Hprp3p interacts with Hprp4p. J Biol Chem 277:23764–23772

    PubMed  CAS  Google Scholar 

  170. Heng HH, Wang A, Hu J (1998) Mapping of the human HPRP3 and HPRP4 genes encoding U4/U6-associated splicing factors to chromosomes 1q21.1 and 9q31-q33. Genomics 48:273–275

    PubMed  CAS  Google Scholar 

  171. Ayadi L, Callebaut I, Saguez C, Villa T, Mornon JP, Banroques J (1998) Functional and structural characterization of the prp3 binding domain of the yeast prp4 splicing factor. J Mol Biol 284:673–687

    PubMed  CAS  Google Scholar 

  172. Lauber J, Plessel G, Prehn S, Will CL, Fabrizio P, Gröning K, Lane WS, Lührmann R (1997) The human U4/U6 snRNP contains 60 and 90kD proteins that are structurally homologous to the yeast splicing factors Prp4p and Prp3p. RNA 3:926–941

    PubMed  CAS  Google Scholar 

  173. Linder B, Dill H, Hirmer A, Brocher J, Lee GP, Mathavan S, Bolz HJ, Winkler C, Laggerbauer B, Fischer U (2011) Systemic splicing factor deficiency causes tissue-specific defects: a zebrafish model for retinitis pigmentosa. Hum Mol Genet 20:368–377

    PubMed  CAS  Google Scholar 

  174. Schmidt-Kastner R, Yamamoto H, Hamasaki D, Yamamoto H, Parel JM, Schmitz C, Dorey CK, Blanks JC, Preising MN (2008) Hypoxia-regulated components of the U4/U6.U5 tri-small nuclear riboprotein complex: possible role in autosomal dominant retinitis pigmentosa. Mol Vis 14:125–135

    PubMed  CAS  Google Scholar 

  175. Zhou A, Ou AC, Cho A, Benz EJ Jr, Huang SC (2008) Novel splicing factor RBM25 modulates Bcl-x pre-mRNA 5′ splice site selection. Mol Cell Biol 28:5924–5936

    PubMed  CAS  Google Scholar 

  176. Kanhoush R, Beenders B, Perrin C, Moreau J, Bellini M, Penrad-Mobayed M (2010) Novel domains in the hnRNP G/RBMX protein with distinct roles in RNA binding and targeting nascent transcripts. Nucleus 1:109–122

    PubMed  Google Scholar 

  177. Kanhoush R, Praseuth D, Perrin C, Chardard D, Vinh J, Penrad-Mobayed M (2011) Differential RNA-binding activity of the hnRNP G protein correlated with the sex genotype in the amphibian oocyte. Nucleic Acids Res 39:4109–4121

    PubMed  CAS  Google Scholar 

  178. Adamik B, Islam A, Rouhani FN, Hawari FI, Zhang J, Levine SJ (2008) An association between RBMX, a heterogeneous nuclear ribonucleoprotein, and ARTS-1 regulates extracellular TNFR1 release. Biochem Biophys Res Commun 371:505–509

    PubMed  CAS  Google Scholar 

  179. Elliott DJ (2004) The role of potential splicing factors including RBMY, RBMX, hnRNPG-T and STAR proteins in spermatogenesis. Int J Androl 27:328–334

    PubMed  CAS  Google Scholar 

  180. Sumanasekera C, Kelemen O, Beullens M, Aubol BE, Adams JA, Sunkara M, Morris A, Bollen M, Andreadis A, Stamm S (2012) C6 pyridinium ceramide influences alternative pre-mRNA splicing by inhibiting protein phosphatase-1. Nucleic Acids Res 40:4025–4039

    PubMed  CAS  Google Scholar 

  181. Landeras-Bueno S, Jorba N, Pérez-Cidoncha M, Ortín J (2011) The splicing factor proline-glutamine rich (SFPQ/PSF) is involved in influenza virus transcription. PLoS Pathog 7:e1002397

    PubMed  CAS  Google Scholar 

  182. Kunde SA, Musante L, Grimme A, Fischer U, Müller E, Wanker EE, Kalscheuer VM (2011) The X-chromosome-linked intellectual disability protein PQBP1 is a component of neuronal RNA granules and regulates the appearance of stress granules. Hum Mol Genet 20:4916–4931

    PubMed  CAS  Google Scholar 

  183. Cristobo I, Larriba MJ, Ríos Vde L, García F, Muñoz A, Casal JI (2011) Proteomic analysis of 1α,25-dihydroxyvitamin D(3) action on human colon cancer cells reveals a link to splicing regulation. J Proteomics 75:384–397

    PubMed  CAS  Google Scholar 

  184. Ha K, Takeda Y, Dynan WS (2011) Sequences in PSF/SFPQ mediate radioresistance and recruitment of PSF/SFPQ-containing complexes to DNA damage sites in human cells. DNA Repair 10(3):252–259

    PubMed  CAS  Google Scholar 

  185. Rajesh C, Baker DK, Pierce AJ, Pittman DL (2011) The splicing-factor related protein SFPQ/PSF interacts with RAD51D and is necessary for homology-directed repair and sister chromatid cohesion. Nucleic Acids Res 3:132–145

    Google Scholar 

  186. Salton M, Lerenthal Y, Wang SY, Chen DJ, Shiloh Y (2010) Involvement of Matrin 3 and SFPQ/NONO in the DNA damage response. Cell Cycle 9:1568–1576

    PubMed  CAS  Google Scholar 

  187. Herrmann A, Fleischer K, Czajkowska H, Müller-Newen G, Becker W (2007) Characterization of cyclin L1 as an immobile component of the splicing factor compartment. FASEB J 21:3142–3152

    PubMed  CAS  Google Scholar 

  188. de Graaf K, Hekerman P, Spelten O, Herrmann A, Packman LC, Büssow K, Müller-Newen G, Becker W (2004) Characterization of cyclin L2, a novel cyclin with an arginine/serine-rich domain: phosphorylation by DYRK1A and colocalization with splicing factors. J Biol Chem 279:4612–4624

    PubMed  Google Scholar 

  189. Bond CS, Fox AH (2009) Paraspeckles: nuclear bodies built on long noncoding RNA. J Cell Biol 186:637–644

    PubMed  CAS  Google Scholar 

  190. Loyer P, Trembley JH, Grenet JA, Busson A, Corlu A, Zhao W, Kocak M, Kidd VJ, Lahti JM (2008) Characterization of cyclin L1 and L2 interactions with CDK11 and splicing factors: influence of cyclin L isoforms on splice site selection. J Biol Chem 283:7721–7732

    PubMed  CAS  Google Scholar 

  191. Li HL, Wang TS, Li XY, Li N, Huang DZ, Chen Q, Ba Y (2007) Overexpression of cyclin L2 induces apoptosis and cell-cycle arrest in human lung cancer cells. Chin Med J (Engl) 120:905–909

    CAS  Google Scholar 

  192. Zhuo L, Gong J, Yang R, Sheng Y, Zhou L, Kong X, Cao K (2009) Inhibition of proliferation and differentiation and promotion of apoptosis by cyclin L2 in mouse embryonic carcinoma P19 cells. Biochem Biophys Res Commun 390:451–457

    PubMed  CAS  Google Scholar 

  193. Peng L, Yanjiao M, Ai-guo W, Pengtao G, Jianhua L, Ju Y, Hongsheng O, Xichen Z (2011) A fine balance between CCNL1 and TIMP1 contributes to the development of breast cancer cells. Biochem Biophys Res Commun 409:344–349

    PubMed  Google Scholar 

  194. Tannukit S, Wen X, Wang H, Paine ML (2008) TFIP11, CCNL1 and EWSR1 protein-protein interactions, and their nuclear localization. Int J Mol Sci 9:1504–1514

    PubMed  CAS  Google Scholar 

  195. Muller D, Millon R, Théobald S, Hussenet T, Wasylyk B, du Manoir S, Abecassis J (2006) Cyclin L1 (CCNL1) gene alterations in human head and neck squamous cell carcinoma. Br J Cancer 94:1041–1044

    PubMed  CAS  Google Scholar 

  196. Chen HH, Wang YC, Fann MJ (2006) Identification and characterization of the CDK12/cyclin L1 complex involved in alternative splicing regulation. Mol Cell Biol 26:2736–2745

    PubMed  CAS  Google Scholar 

  197. Redon R, Hussenet T, Bour G, Caulee K, Jost B, Muller D, Abecassis J, du Manoir S (2002) Amplicon mapping and transcriptional analysis pinpoint cyclin L as a candidate oncogene in head and neck cancer. Cancer Res 62:6211–6217

    PubMed  CAS  Google Scholar 

  198. Russo J, Tay LK, Russo IH (1982) Differentiation of the mammary gland and susceptibility to carcinogenesis. Breast Cancer Res Treat 2:5–73

    PubMed  CAS  Google Scholar 

  199. Russo J, Balogh GA, Chen J, Fernandez SV, Fernbaugh R, Heulings R, Mailo DA, Moral R, Russo PA, Sheriff F, Vanegas JE, Wang R, Russo IH (2006) The concept of stem cell in the mammary gland and its implication in morphogenesis, cancer and prevention. Front Biosci 11:151–172

    PubMed  CAS  Google Scholar 

  200. Russo J, Tait L, Russo IH (1983) Susceptibility of the mammary gland to carcinogenesis. III. The cell of origin of rat mammary carcinoma. Am J Pathol 113:50–66

    PubMed  CAS  Google Scholar 

  201. Russo IH, Russo J (1978) Developmental stage of the rat mammary gland as determinant of its susceptibility to 7,12-dimethylbenz[a]anthracene. J Natl Cancer Inst 61:1439–1449

    PubMed  CAS  Google Scholar 

  202. Russo IH, Koszalka M, Russo J (1991) Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis. Br J Cancer 64:481–484

    PubMed  CAS  Google Scholar 

  203. Russo J, Russo IH (1998) Differentiation and breast cancer development. In: Heppner G (ed) Advances in oncobiology. JAI Press, Greenwich, CN, pp 1–10

    Google Scholar 

  204. Russo J, Russo IH (1997) Toward a unified concept of mammary carcinogenesis. Prog Clin Biol Res 396:1–16

    PubMed  CAS  Google Scholar 

  205. Russo J, Ao X, Grill C, Russo IH (1999) Pattern of distribution of cells positive for estrogen receptor alpha and progesterone receptor in relation to proliferating cells in the mammary gland. Breast Cancer Res Treat 53:217–227

    PubMed  CAS  Google Scholar 

  206. Russo J, Mailo D, Hu YF, Balogh G, Sheriff F, Russo IH (2005) Breast differentiation and its implication in cancer prevention. Clin Cancer Res 11:931s–936s

    PubMed  CAS  Google Scholar 

  207. Salomonis N, Schlieve CR, Pereira L, Wahlquist C, Colas A, Zambon AC, Vranizan K, Spindler MJ, Pico AR, Cline MS, Clark TA, Williams A, Blume JE, Samal E, Mercola M, Merrill BJ, Conklin BR (2010) Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation. Proc Natl Acad Sci U S A 107:10514–10519

    PubMed  CAS  Google Scholar 

  208. Salomonis N, Nelson B, Vranizan K, Pico AR, Hanspers K, Kuchinsky A, Ta L, Mercola M, Conklin BR (2009) Alternative splicing in the differentiation of human embryonic stem cells into cardiac precursors. PLoS Comput Biol 5:e1000553

    PubMed  Google Scholar 

  209. Brooks YS, Wang G, Yang Z, Smith KK, Bieberich E, Ko L (2009) Functional pre-mRNA trans-splicing of coactivator CoAA and corepressor RBM4 during stem/progenitor cell differentiation. J Biol Chem 284:18033–18046

    PubMed  CAS  Google Scholar 

  210. Yeo GW, Coufal NG, Liang TY, Peng GE, Fu XD, Gage FH (2009) An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells. Nat Struct Mol Biol 16:130–137

    PubMed  CAS  Google Scholar 

  211. Bunaciu RP, Tang T, Mao CD (2008) Differential expression of Wnt13 isoforms during leukemic cell differentiation. Oncol Rep 20:195–201

    PubMed  CAS  Google Scholar 

  212. Robinett CC, Vaughan AG, Knapp JM, Baker BS (2010) Sex and the single cell. II. There is a time and place for sex. PLoS Biol 8:e1000365

    PubMed  Google Scholar 

  213. Alam AH, Suzuki H, Tsukahara T (2010) Retinoic acid treatment and cell aggregation independently regulate alternative splicing in P19 cells during neural differentiation. Cell Biol Int 34:631–643

    PubMed  CAS  Google Scholar 

  214. Moors M, Vudattu NK, Abel J, Krämer U, Rane L, Ulfig N, Ceccatelli S, Seyfert-Margolies V, Fritsche E, Maeurer MJ (2010) Interleukin-7 (IL-7) and IL-7 splice variants affect differentiation of human neural progenitor cells. Genes Immun 11:11–20

    PubMed  CAS  Google Scholar 

  215. Piprek RP (2009) Genetic mechanisms underlying male sex determination in mammals. J Appl Genet 50:347–360

    PubMed  CAS  Google Scholar 

  216. Clower CV, Chatterjee D, Wang Z, Cantley LC, Vander Heiden MG, Krainer AR (2010) The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc Natl Acad Sci U S A 107:1894–1899

    PubMed  CAS  Google Scholar 

  217. Gillett A, Maratou K, Fewings C, Harris RA, Jagodic M, Aitman T, Olsson T (2009) Alternative splicing and transcriptome profiling of experimental autoimmune encephalomyelitis using genome-wide exon arrays. PLoS One 4:e7773

    PubMed  Google Scholar 

  218. Kobayashi E, Shimizu R, Kikuchi Y, Takahashi S, Yamamoto M (2010) Loss of the Gata1 gene IE exon leads to variant transcript expression and the production of a GATA1 protein lacking the N-terminal domain. J Biol Chem 285:773–783

    PubMed  CAS  Google Scholar 

  219. Peri P, López de Cicco R, Santucci-Pereira J, Slifker M, Ross EA, Russo IH, Russo PA, Arslan AA, Belitskaya-Lévy I, Zeleniuch-Jacquotte A, Bordas P, Lenner P, Åhman J, Afanasyeva Y, Johansson R, Sheriff F, Hallmans G, Toniolo P, Russo J (2012) Defining the genomic signature of the parous breast. BMC Med Genomic

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Jose Russo & Irma H. Russo

Authors
  1. Jose Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irma H. Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Russo, J., Russo, I.H. (2013). The Role of Spliceosome in the Human Breast. In: Role of the Transcriptome in Breast Cancer Prevention. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4884-6_8

Download citation

Publish with us

Policies and ethics

Search

Navigation