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Long Noncoding RNAs and Their Applications: Focus on Architectural RNA (arcRNA), a Class of lncRNA

  • Tomohiro Yamazaki
Chapter

Abstract

Transcriptome analyses have revealed large numbers of non-protein coding transcripts called noncoding RNAs (ncRNAs), which are produced from most genomic regions in mammalian cells. These ncRNAs include many thousands of long noncoding RNAs (lncRNAs) more than 200 nucleotides in length. Although our knowledge of these lncRNAs remains limited, recent studies have revealed their diverse roles under physiological and pathological conditions, as well as their mechanisms of action in a variety of cellular processes including epigenetic regulation, transcriptional regulation, posttranscriptional processing, and intracellular organization. In addition, multiple studies show that aberrant expression of lncRNAs is associated with various diseases, including cancer and neurodegenerative disorders, suggesting that lncRNAs represent promising target molecules for biomedical applications. Here, I review lncRNAs and several related applications and in particular an emerging class of lncRNAs termed architectural RNA (arcRNA). I describe and discuss arcRNAs in mammals, focusing on their biogenesis, mechanisms of action, and potential applications. In addition, I highlight our newly established methods for discovering arcRNA candidates. Finally, I emphasize the importance of identifying the RNA elements embedded in lncRNAs that dictate their functions; these elements provide opportunities for future applications in biotechnology, biomarkers, and therapeutics.

Keywords

Long noncoding RNA (lncRNA) Architectural RNA (arcRNA) Nuclear body Semi-extractable RNA (seRNA) NEAT1 Satellite RNA SINEUP Prion-like domain Low-complexity domain Intrinsically disordered domain 

References

  1. Adriaens C, Standaert L, Barra J, Latil M, Verfaillie A, Kalev P, Boeckx B, Wijnhoven PW, Radaelli E, Vermi W, Leucci E, Lapouge G, Beck B, van den Oord J, Nakagawa S, Hirose T, Sablina AA, Lambrechts D, Aerts S, Blanpain C, Marine JC (2016) p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity. Nat Med 22:861–868PubMedCrossRefGoogle Scholar
  2. Aguzzi A, Altmeyer M (2016) Phase separation: linking cellular compartmentalization to disease. Trends Cell Biol 26:547–558PubMedCrossRefGoogle Scholar
  3. Alberti S, Hyman AA (2016) Are aberrant phase transitions a driver of cellular aging? BioEssays 38:959–968PubMedPubMedCentralCrossRefGoogle Scholar
  4. Anderson DM, Anderson KM, Chang CL, Makarewich CA, Nelson BR, McAnally JR, Kasaragod P, Shelton JM, Liou J, Bassel-Duby R, Olson EN (2015) A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell 160:595–606PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, Evantal N, Memczak S, Rajewsky N, Kadener S (2014) circRNA biogenesis competes with pre-mRNA splicing. Mol Cell 56:55–66PubMedCrossRefGoogle Scholar
  6. Audas TE, Jacob MD, Lee S (2012a) Immobilization of proteins in the nucleolus by ribosomal intergenic spacer noncoding RNA. Mol Cell 45:147–517PubMedCrossRefGoogle Scholar
  7. Audas TE, Jacob MD, Lee S (2012b) The nucleolar detention pathway: a cellular strategy for regulating molecular networks. Cell Cycle 11:2059–2062PubMedPubMedCentralCrossRefGoogle Scholar
  8. Audas TE, Audas DE, Jacob MD, Ho JJ, Khacho M, Wang M, Perera JK, Gardiner C, Bennett CA, Head T, Kryvenko ON, Jorda M, Daunert S, Malhotra A, Trinkle-Mulcahy L, Gonzalgo ML, Lee S (2016) Adaptation to stressors by systemic protein amyloidogenesis. Dev Cell 39:155–168PubMedPubMedCentralCrossRefGoogle Scholar
  9. Baltz AG, Munschauer M, Schwanhäusser B, Vasile A, Murakawa Y, Schueler M, Youngs N, Penfold-Brown D, Drew K, Milek M, Wyler E, Bonneau R, Selbach M, Dieterich C, Landthaler M (2012) The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Mol Cell 46:674–690PubMedCrossRefGoogle Scholar
  10. Banani SF, Lee HO, Hyman AA, Rosen MK (2017) Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol 18:285–298PubMedCrossRefGoogle Scholar
  11. Barry G, Briggs JA, Hwang DW, Nayler SP, Fortuna PR, Jonkhout N, Dachet F, Maag JL, Mestdagh P, Singh EM, Avesson L, Kaczorowski DC, Ozturk E, Jones NC, Vetter I, Arriola-Martinez L, Hu J, Franco GR, Warn VM, Gong A, Dinger ME, Rigo F, Lipovich L, Morris MJ, O'Brien TJ, Lee DS, Loeb JA, Blackshaw S, Mattick JS, Wolvetang EJ (2017) The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states. Sci Rep 7:40127PubMedPubMedCentralCrossRefGoogle Scholar
  12. Batista PJ, Chang HY (2013) Long noncoding RNAs: cellular address codes in development and disease. Cell 152:1298–1307PubMedPubMedCentralCrossRefGoogle Scholar
  13. Belzil VV, Gendron TF, Petrucelli L (2013) RNA-mediated toxicity in neurodegenerative disease. Mol Cell Neurosci 56:406–419PubMedCrossRefGoogle Scholar
  14. Bertone P, Stolc V, Royce TE, Rozowsky JS, Urban AE, Zhu X, Rinn JL, Tongprasit W, Samanta M, Weissman S, Gerstein M, Snyder M (2004) Global identification of human transcribed sequences with genome tiling arrays. Science 306:2242–2246PubMedCrossRefGoogle Scholar
  15. Biamonti G (2004) Nuclear stress bodies: a heterochromatin affair? Nat Rev Mol Cell Biol 5:493–498PubMedCrossRefGoogle Scholar
  16. Biamonti G, Vourc’h C (2010) Nuclear stress bodies. Cold Spring Harb Perspect Biol 2:a000695PubMedPubMedCentralCrossRefGoogle Scholar
  17. Blume CJ, Hotz-Wagenblatt A, Hüllein J, Sellner L, Jethwa A, Stolz T, Slabicki M, Lee K, Sharathchandra A, Benner A, Dietrich S, Oakes CC, Dreger P, te Raa D, Kater AP, Jauch A, Merkel O, Oren M, Hielscher T, Zenz T (2015) p53-dependent non-coding RNA networks in chronic lymphocytic leukemia. Leukemia 29:2015–2023PubMedCrossRefGoogle Scholar
  18. Brown JA, Valenstein ML, Yario TA, Tycowski KT, Steitz JA (2012) Formation of triple-helical structures by the 3′-end sequences of MALAT1 and MENβ noncoding RNAs. Proc Natl Acad Sci U S A 109:19202–19207PubMedPubMedCentralCrossRefGoogle Scholar
  19. Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schönbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y, FANTOM Consortium, RIKEN Genome Exploration Research Group, GenomeScience Group (Genome Network Project Core Group) (2005) The transcriptional landscape of the mammalian genome. Science 309:1559–1563PubMedCrossRefGoogle Scholar
  20. Carrieri C, Cimatti L, Biagioli M, Beugnet A, Zucchelli S, Fedele S, Pesce E, Ferrer I, Collavin L, Santoro C, Forrest AR, Carninci P, Biffo S, Stupka E, Gustincich S (2012) Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 491:454–457PubMedCrossRefGoogle Scholar
  21. Castello A, Fischer B, Eichelbaum K, Horos R, Beckmann BM, Strein C, Davey NE, Humphreys DT, Preiss T, Steinmetz LM, Krijgsveld J, Hentze MW (2012) Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 149:1393–1406PubMedCrossRefGoogle Scholar
  22. Castello A, Fischer B, Frese CK, Horos R, Alleaume AM, Foehr S, Curk T, Krijgsveld J, Hentze MW (2016) Comprehensive identification of RNA-binding domains in human cells. Mol Cell 63:696–710PubMedPubMedCentralCrossRefGoogle Scholar
  23. Cech TR, Steitz JA (2014) The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157:77–94PubMedCrossRefGoogle Scholar
  24. Chakravarty D, Sboner A, Nair SS, Giannopoulou E, Li R, Hennig S, Mosquera JM, Pauwels J, Park K, Kossai M, MacDonald TY, Fontugne J, Erho N, Vergara IA, Ghadessi M, Davicioni E, Jenkins RB, Palanisamy N, Chen Z, Nakagawa S, Hirose T, Bander NH, Beltran H, Fox AH, Elemento O, Rubin MA (2014) The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nat Commun 5:5383PubMedPubMedCentralCrossRefGoogle Scholar
  25. Chen LL (2016a) The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol 17:205–211PubMedCrossRefGoogle Scholar
  26. Chen LL (2016b) Linking long noncoding RNA localization and function. Trends Biochem Sci 41:761–772PubMedCrossRefGoogle Scholar
  27. Chen LL, Carmichael GG (2009) Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA. Mol Cell 35:467–478PubMedPubMedCentralCrossRefGoogle Scholar
  28. Chen CK, Blanco M, Jackson C, Aznauryan E, Ollikainen N, Surka C, Chow A, Cerase A, McDonel P, Guttman M (2016) Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing. Science 354:468–472PubMedCrossRefGoogle Scholar
  29. Chiodi I, Biggiogera M, Denegri M, Corioni M, Weighardt F, Cobianchi F, Riva S, Biamonti G (2000) Structure and dynamics of hnRNP-labelled nuclear bodies induced by stress treatments. J Cell Sci 113(Pt 22):4043–4053PubMedGoogle Scholar
  30. Chiodi I, Corioni M, Giordano M, Valgardsdottir R, Ghigna C, Cobianchi F, Xu RM, Riva S, Biamonti G (2004) RNA recognition motif 2 directs the recruitment of SF2/ASF to nuclear stress bodies. Nucleic Acids Res 32:4127–4136PubMedPubMedCentralCrossRefGoogle Scholar
  31. Choo KH, Earle E, Mcquikkan C (1990) A homologous subfamily of satellite III DNA on human chromosomes 14 and 22. Nucleic Acids Res 18:5641–5648PubMedPubMedCentralCrossRefGoogle Scholar
  32. Choudhry H, Schödel J, Oikonomopoulos S, Camps C, Grampp S, Harris AL, Ratcliffe PJ, Ragoussis J, Mole DR (2014) Extensive regulation of the non-coding transcriptome by hypoxia: role of HIF in releasing paused RNApol2. EMBO Rep 15:70–76PubMedCrossRefGoogle Scholar
  33. Choudhry H, Albukhari A, Morotti M, Haider S, Moralli D, Smythies J, Schödel J, Green CM, Camps C, Buffa F, Ratcliffe P, Ragoussis J, Harris AL, Mole DR (2015) Tumor hypoxia induces nuclear paraspeckle formation through HIF-2alpha dependent transcriptional activation of NEAT1 leading to cancer cell survival. Oncogene 34:4546PubMedCrossRefGoogle Scholar
  34. Chu C, Zhang QC, da Rocha ST, Flynn RA, Bharadwaj M, Calabrese JM, Magnuson T, Heard E, Chang HY (2015) Systematic discovery of Xist RNA binding proteins. Cell 161:404–416PubMedPubMedCentralCrossRefGoogle Scholar
  35. Chujo T, Yamazaki T, Hirose T (2016) Architectural RNAs (arcRNAs): a class of long noncoding RNAs that function as the scaffold of nuclear bodies. Biochim Biophys Acta 1859:139–146PubMedCrossRefGoogle Scholar
  36. Chujo T, Yamazaki T, Kawaguchi T, Kurosaka S, Takumi T, Nakagawa S, Hirose T (2017) Unusual semi-extractability as a hallmark of nuclear body-associated architectural noncoding RNAs. EMBO J 36:1447–1462PubMedCrossRefGoogle Scholar
  37. Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, Chess A, Lawrence JB (2009) An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell 33:717–726PubMedPubMedCentralCrossRefGoogle Scholar
  38. Conrad NK, Steitz JA (2005) A Kaposi's sarcoma virus RNA element that increases the nuclear abundance of intronless transcripts. EMBO J 24:1831–1841PubMedPubMedCentralCrossRefGoogle Scholar
  39. Cotto J, Fox S, Morimoto R (1997) HSF1 granules: a novel stress-induced nuclear compartment of human cells. J Cell Sci 110(Pt 23):2925–2934PubMedGoogle Scholar
  40. Courchaine EM, Lu A, Neugebauer KM (2016) Droplet organelles? EMBO J 35:1603–1612PubMedPubMedCentralCrossRefGoogle Scholar
  41. Denegri M, Moralli D, Rocchi M, Biggiogera M, Raimondi E, Cobianchi F, De Carli L, Riva S, Biamonti G (2002) Human chromosomes 9, 12, and 15 contain the nucleation sites of stress-induced nuclear bodies. Mol Biol Cell 13:2069–2079PubMedPubMedCentralCrossRefGoogle Scholar
  42. Engreitz JM, Haines JE, Perez EM, Munson G, Chen J, Kane M, McDonel PE, Guttman M, Lander ES (2016a) Local regulation of gene expression by lncRNA promoters, transcription and splicing. Nature 539:452–455PubMedCrossRefGoogle Scholar
  43. Engreitz JM, Ollikainen N, Guttman M (2016b) Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression. Nat Rev Mol Cell Biol 17:756–770PubMedCrossRefGoogle Scholar
  44. Engström PG, Suzuki H, Ninomiya N, Akalin A, Sessa L, Lavorgna G, Brozzi A, Luzi L, Tan SL, Yang L, Kunarso G, Ng EL, Batalov S, Wahlestedt C, Kai C, Kawai J, Carninci P, Hayashizaki Y, Wells C, Bajic VB, Orlando V, Reid JF, Lenhard B, Lipovich L (2006) Complex Loci in human and mouse genomes. PLoS Genet 2:e47PubMedPubMedCentralCrossRefGoogle Scholar
  45. Enukashvily NI, Donev R, Waisertreiger IS, Podgornaya OI (2007) Human chromosome 1 satellite 3 DNA is decondensed, demethylated and transcribed in senescent cells and in A431 epithelial carcinoma cells. Cytogenet Genome Res 118:42–54PubMedCrossRefGoogle Scholar
  46. Fong KW, Li Y, Wang W, Ma W, Li K, Qi RZ, Liu D, Songyang Z, Chen J (2013) Whole-genome screening identifies proteins localized to distinct nuclear bodies. J Cell Biol 203:149–164PubMedPubMedCentralCrossRefGoogle Scholar
  47. Fox AH, Lam YW, Leung AK, Lyon CE, Andersen J, Mann M, Lamond AI (2002) Paraspeckles: a novel nuclear domain. Curr Biol 12:13–25PubMedCrossRefGoogle Scholar
  48. Fujimoto A, Furuta M, Totoki Y, Tsunoda T, Kato M, Shiraishi Y, Tanaka H, Taniguchi H, Kawakami Y, Ueno M, Gotoh K, Ariizumi S, Wardell CP, Hayami S, Nakamura T, Aikata H, Arihiro K, Boroevich KA, Abe T, Nakano K, Maejima K, Sasaki-Oku A, Ohsawa A, Shibuya T, Nakamura H, Hama N, Hosoda F, Arai Y, Ohashi S, Urushidate T, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Ojima H, Hiraoka N, Okusaka T, Kubo M, Marubashi S, Yamada T, Hirano S, Yamamoto M, Ohdan H, Shimada K, Ishikawa O, Yamaue H, Chayama K, Miyano S, Aburatani H, Shibata T, Nakagawa H (2016) Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer. Nat Genet 48:500–509PubMedCrossRefGoogle Scholar
  49. Geisler S, Coller J (2013) RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol 14:699–712PubMedPubMedCentralCrossRefGoogle Scholar
  50. Goenka A, Sengupta S, Pandey R, Parihar R, Mohanta GC, Mukerji M, Ganesh S (2016) Human satellite-III non-coding RNAs modulate heat-shock-induced transcriptional repression. J Cell Sci 129:3541–3552PubMedCrossRefGoogle Scholar
  51. Gong C, Maquato LE (2011) lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature 470:284–288PubMedPubMedCentralCrossRefGoogle Scholar
  52. Guarnerio J, Bezzi M, Jeong JC, Paffenholz SV, Berry K, Naldini MM, Lo-Coco F, Tay Y, Beck AH, Pandolfi PP (2016) Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell 165:289–302PubMedCrossRefGoogle Scholar
  53. Guttman M, Rinn JL (2012) Modular regulatory principles of large non-coding RNAs. Nature 482:339–346PubMedPubMedCentralCrossRefGoogle Scholar
  54. Hall LL, Byron M, Carone DM, Whitfield TW, Pouliot GP, Fischer A, Jones P, Lawrence JB (2017) Demethylated HSATII DNA and HSATII RNA foci sequester PRC1 and MeCP2 into cancer-specific nuclear bodies. Cell Rep 18:2943–2956PubMedPubMedCentralCrossRefGoogle Scholar
  55. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388PubMedCrossRefGoogle Scholar
  56. Hennig S, Kong G, Mannen T, Sadowska A, Kobelke S, Blythe A, Knott GJ, Iyer KS, Ho D, Newcombe EA, Hosoki K, Goshima N, Kawaguchi T, Hatters D, Trinkle-Mulcahy L, Hirose T, Bond CS, Fox AH (2015) Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles. J Cell Biol 210:529–539PubMedPubMedCentralCrossRefGoogle Scholar
  57. Hirose T, Mishima Y, Tomari Y (2014a) Elements and machinery of non-coding RNAs: toward their taxonomy. EMBO Rep 15:489–507PubMedPubMedCentralCrossRefGoogle Scholar
  58. Hirose T, Virnicchi G, Tanigawa A, Naganuma T, Li R, Kimura H, Yokoi T, Nakagawa S, Bénard M, Fox AH, Pierron G (2014b) NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies. Mol Biol Cell 25:169–183PubMedPubMedCentralCrossRefGoogle Scholar
  59. Ideue T, Hino K, Kitao S, Yokoi T, Hirose T (2009) Efficient oligonucleotide-mediated degradation of nuclear noncoding RNAs in mammalian cultured cells. RNA 15:1578–1587PubMedPubMedCentralCrossRefGoogle Scholar
  60. Imamura K, Imamachi N, Akizuki G, Kumakura M, Kawaguchi A, Nagata K, Kato A, Kawaguchi Y, Sato H, Yoneda M, Kai C, Yada T, Suzuki Y, Yamada T, Ozawa T, Kaneki K, Inoue T, Kobayashi M, Kodama T, Wada Y, Sekimizu K, Akimitsu N (2014) Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 expression upon immune stimuli. Mol Cell 53:393–406PubMedCrossRefGoogle Scholar
  61. Indrieri A, Grimaldi C, Zucchelli S, Tammaro R, Gustincich S, Franco B (2016) Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo. Sci Rep 6:27315PubMedPubMedCentralCrossRefGoogle Scholar
  62. Jacob MD, Audas TE, Mullineux ST, Lee S (2012) Where no RNA polymerase has gone before: novel functional transcripts derived from the ribosomal intergenic spacer. Nucleus 3:315–319PubMedCrossRefGoogle Scholar
  63. Jacob MD, Audas TE, Uniacke J, Trinkle-Mulcahy L, Lee S (2013) Environmental cues induce a long noncoding RNA-dependent remodeling of the nucleolus. Mol Biol Cell 24:2943–2953PubMedPubMedCentralCrossRefGoogle Scholar
  64. Jolly C, Lakhotia SC (2006) Human sat III and Drosophila hsr omega transcripts: a common paradigm for regulation of nuclear RNA processing in stressed cells. Nucleic Acids Res 34:5508–5514PubMedPubMedCentralCrossRefGoogle Scholar
  65. Kaikkonen MU, Spann NJ, Heinz S, Romanoski CE, Allison KA, Stender JD, Chun HB, Tough DF, Prinjha RK, Benner C, Glass CK (2013) Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription. Mol Cell 51:310–325PubMedPubMedCentralCrossRefGoogle Scholar
  66. Kanadia RN, Johnstone KA, Mankodi A, Lungu C, Thornton CA, Esson D, Timmers AM, Hauswirth WW, Swanson MS (2003) A muscleblind knockout model for myotonic dystrophy. Science 302:1978–1980PubMedPubMedCentralCrossRefGoogle Scholar
  67. Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488PubMedCrossRefGoogle Scholar
  68. Kashi K, Henderson L, Bonetti A, Carninci P (2016) Discovery and functional analysis of lncRNAs: methodologies to investigate an uncharacterized transcriptome. Biochim Biophys Acta 1859:3–15PubMedCrossRefGoogle Scholar
  69. Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J, Suzuki H, Carninci P, Hayashizaki Y, Wells C, Frith M, Ravasi T, Pang KC, Hallinan J, Mattick J, Hume DA, Lipovich L, Batalov S, Engström PG, Mizuno Y, Faghihi MA, Sandelin A, Chalk AM, Mottagui-Tabar S, Liang Z, Lenhard B, Wahlestedt C, RIKEN Genome Exploration Research Group, Genome Science Group (Genome Network Project Core Group), FANTOM Consortium (2005) Antisense transcription in the mammalian transcriptome. Science 309:1564–1566PubMedCrossRefGoogle Scholar
  70. Kawaguchi T, Hirose T (2015) Chromatin remodeling complexes in the assembly of long noncoding RNA-dependent nuclear bodies. Nucleus 6:462–467PubMedPubMedCentralCrossRefGoogle Scholar
  71. Kawaguchi T, Tanigawa A, Naganuma T, Ohkawa Y, Souquere S, Pierron G, Hirose T (2015) SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies. Proc Natl Acad Sci U S A 112:4304–4309PubMedPubMedCentralCrossRefGoogle Scholar
  72. Kishikawa T, Otsuka M, Yoshikawa T, Ohno M, Yamamoto K, Yamamoto N, Kotani A, Koike K (2016) Quantitation of circulating satellite RNAs in pancreatic cancer patients. JCI Insight 1:e86646PubMedPubMedCentralCrossRefGoogle Scholar
  73. Kretz M, Siprashvili Z, Chu C, Webster DE, Zehnder A, Qu K, Lee CS, Flockhart RJ, Groff AF, Chow J, Johnston D, Kim GE, Spitale RC, Flynn RA, Zheng GX, Aiyer S, Raj A, Rinn JL, Chang HY, Khavari PA (2013) Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493:231–235PubMedCrossRefGoogle Scholar
  74. Lee M, Sadowska A, Bekere I, Ho D, Gully BS, Lu Y, Iyer KS, Trewhella J, Fox AH, Bond CS (2015) The structure of human SFPQ reveals a coiled-coil mediated polymer essential for functional aggregation in gene regulation. Nucleic Acids Res 43:3826–3840PubMedPubMedCentralCrossRefGoogle Scholar
  75. Lee S, Kopp F, Chang TC, Sataluri A, Chen B, Sivakumar S, Yu H, Xie Y, Mendell JT (2016) Noncoding RNA NORAD regulates genomic stability by sequestering PUMILIO proteins. Cell 164:69–80PubMedCrossRefGoogle Scholar
  76. Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O, Fatica A, Santini T, Andronache A, Wade M, Laneve P, Rajewsky N, Bozzoni I (2017) Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol Cell 66:22–37PubMedPubMedCentralCrossRefGoogle Scholar
  77. Li R, Harvey AR, Hodgetts SI, Fox AH (2017) Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1_1 isoform outside paraspeckles. RNA 23:872–881PubMedPubMedCentralCrossRefGoogle Scholar
  78. Liang D, Wilusz JE (2014) Short intronic repeat sequences facilitate circular RNA production. Genes Dev 28:2233–2247PubMedPubMedCentralCrossRefGoogle Scholar
  79. Liu SJ, Horlbeck MA, Cho SW, Birk HS, Malatesta M, He D, Attenello FJ, Villalta JE, Cho MY, Chen Y, Mandegar MA, Olvera MP, Gilbert LA, Conklin BR, Chang HY, Weissman JS, Lim DA (2017) CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells. Science 355:aah7111PubMedCrossRefGoogle Scholar
  80. Lu Z, Chang HY (2016) Decoding the RNA structurome. Curr Opin Struct Biol 36:142–148PubMedPubMedCentralCrossRefGoogle Scholar
  81. Ma H, Han P, Ye W, Chen H, Zheng X, Cheng L, Zhang L, Yu L, Wu X, Xu Z, Lei Y, Zhang F (2017) The long noncoding RNA NEAT1 exerts antihantaviral effects by acting as positive feedback for RIG-I signaling. J Virol 91:e02250–e02216PubMedPubMedCentralGoogle Scholar
  82. Mannen T, Yamashita S, Tomita K, Goshima N, Hirose T (2016) The Sam68 nuclear body is composed of two RNase-sensitive substructures joined by the adaptor HNRNPL. J Cell Biol 214:45–59PubMedPubMedCentralCrossRefGoogle Scholar
  83. Mao YS, Sunwoo H, Zhang B, Spector DL (2011) Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nat Cell Biol 13:95–101PubMedCrossRefGoogle Scholar
  84. Matsumoto A, Pasut A, Matsumoto M, Yamashita R, Fung J, Monteleone E, Saghatelian A, Nakayama KI, Clohessy JG, Pandolfi PP (2017) mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature 541:228–232PubMedCrossRefGoogle Scholar
  85. McHugh CA, Chen CK, Chow A, Surka CF, Tran C, McDonel P, Pandya-Jones A, Blanco M, Burghard C, Moradian A, Sweredoski MJ, Shishkin AA, Su J, Lander ES, Hess S, Plath K, Guttman M (2015) The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature 521:232–236PubMedPubMedCentralCrossRefGoogle Scholar
  86. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–338PubMedCrossRefGoogle Scholar
  87. Mohan A, Goodwin M, Swanson MS (2014) RNA-protein interactions in unstable microsatellite diseases. Brain Res 1584:3–14PubMedCrossRefGoogle Scholar
  88. Naganuma T, Nakagawa S, Tanigawa A, Sasaki YF, Goshima N, Hirose T (2012) Alternative 3′-end processing of long noncoding RNA initiates construction of nuclear paraspeckles. EMBO J 31:4020–4034PubMedPubMedCentralCrossRefGoogle Scholar
  89. Nakagawa S, Naganuma T, Shioi G, Hirose T (2011) Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice. J Cell Biol 193:31–39PubMedPubMedCentralCrossRefGoogle Scholar
  90. Nakagawa S, Shimada M, Yanaka K, Mito M, Arai T, Takahashi E, Fujita Y, Fujimori T, Standaert L, Marine JC, Hirose T (2014) The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice. Development 141:4618–4627PubMedPubMedCentralCrossRefGoogle Scholar
  91. Nelson DL, Orr HT, Warren ST (2013) The unstable repeats--three evolving faces of neurological disease. Neuron 77:825–843PubMedPubMedCentralCrossRefGoogle Scholar
  92. Nelson BR, Makarewich CA, Anderson DM, Winders BR, Troupes CD, Wu F, Reese AL, McAnally JR, Chen X, Kavalali ET, Cannon SC, Houser SR, Bassel-Duby R, Olson EN (2016) A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science 351:271–275PubMedPubMedCentralCrossRefGoogle Scholar
  93. Nishimoto Y, Nakagawa S, Hirose T, Okano HJ, Takao M, Shibata S, Suyama S, Kuwako K, Imai T, Murayama S, Suzuki N, Okano H (2013) The long non-coding RNA nuclear-enriched abundant transcript 1_2 induces paraspeckle formation in the motor neuron during the early phase of amyotrophic lateral sclerosis. Mol Brain 6:31PubMedPubMedCentralCrossRefGoogle Scholar
  94. Paralkar VR, Taborda CC, Huang P, Yao Y, Kossenkov AV, Prasad R, Luan J, Davies JO, Hughes JR, Hardison RC, Blobel GA, Weiss MJ (2016) Unlinking an lncRNA from its associated cis element. Mol Cell 62:104–110PubMedPubMedCentralCrossRefGoogle Scholar
  95. Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, Fox AH, Bond CS (2012) Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proc Natl Acad Sci U S A 109:4846–4850PubMedPubMedCentralCrossRefGoogle Scholar
  96. Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641PubMedCrossRefGoogle Scholar
  97. Prasanth KV, Prasanth SG, Xuan Z, Hearn S, Freier SM, Bennett CF, Zhang MQ, Spector DL (2005) Regulating gene expression through RNA nuclear retention. Cell 123:249–263PubMedCrossRefGoogle Scholar
  98. Quinn JJ, Chang HY (2016) Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 17:47–62PubMedCrossRefGoogle Scholar
  99. Ramaswami M, Taylor JP, Parker R (2013) Altered ribostasis: RNA-protein granules in degenerative disorders. Cell 154:727–736PubMedCrossRefGoogle Scholar
  100. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166PubMedCrossRefGoogle Scholar
  101. Saha S, Sugumar P, Bhandari P, Rangarajan PN (2006) Identification of Japanese encephalitis virus-inducible genes in mouse brain and characterization of GARG39/IFIT2 as a microtubule-associated protein. J Gen Virol 87:3285–3289PubMedCrossRefGoogle Scholar
  102. Salzman J (2016) Circular RNA expression: its potential regulation and function. Trends Genet 32:309–316PubMedPubMedCentralCrossRefGoogle Scholar
  103. Sarma K, Levasseur P, Aristarkhov A, Lee JT (2010) Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of Xist RNA localization to the X chromosome. Proc Natl Acad Sci U S A 107:22196–22201PubMedPubMedCentralCrossRefGoogle Scholar
  104. Sasaki YT, Ideue T, Sano M, Mituyama T, Hirose T (2009) MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proc Natl Acad Sci U S A 106:2525–2530PubMedPubMedCentralCrossRefGoogle Scholar
  105. Schmitt AM, Chang HY (2016) Long noncoding RNAs in cancer pathways. Cancer Cell 29:452–463PubMedPubMedCentralCrossRefGoogle Scholar
  106. Shen W, Liang XH, Crooke ST (2014) Phosphorothioate oligonucleotides can displace NEAT1 RNA and form nuclear paraspeckle-like structures. Nucleic Acids Res 42:8648–8662PubMedPubMedCentralCrossRefGoogle Scholar
  107. Shevtsov SP, Dundr M (2011) Nucleation of nuclear bodies by RNA. Nat Cell Biol 13:167–173PubMedCrossRefGoogle Scholar
  108. Souquere S, Beauclair G, Harper F, Fox A, Pierron G (2010) Highly ordered spatial organization of the structural long noncoding NEAT1 RNAs within paraspeckle nuclear bodies. Mol Biol Cell 21:4020–4027PubMedPubMedCentralCrossRefGoogle Scholar
  109. Standaert L, Adriaens C, Radaelli E, Van Keymeulen A, Blanpain C, Hirose T, Nakagawa S, Marine JC (2014) The long noncoding RNA Neat1 is required for mammary gland development and lactation. RNA 20:1844–1849PubMedPubMedCentralCrossRefGoogle Scholar
  110. Steitz J (2015) RNA-RNA base-pairing: theme and variations. RNA 21:476–477PubMedPubMedCentralCrossRefGoogle Scholar
  111. Sunwoo H, Dinger ME, Wilusz JE, Amaral PP, Mattick JS, Spector DL (2009) MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res 19:347–359PubMedPubMedCentralCrossRefGoogle Scholar
  112. Sunwoo JS, Lee ST, Im W, Lee M, Byun JI, Jung KH, Park KI, Jung KY, Lee SK, Chu K, Kim M (2017) Altered expression of the long noncoding RNA NEAT1 in Huntington’s disease. Mol Neurobiol 54:1577–1586PubMedCrossRefGoogle Scholar
  113. Takahashi H, Carninci P (2014) Widespread genome transcription: new possibilities for RNA therapies. Biochem Biophys Res Commun 452:294–301PubMedCrossRefGoogle Scholar
  114. Taniue K, Kurimoto A, Sugimasa H, Nasu E, Takeda Y, Iwasaki K, Nagashima T, Okada-Hatakeyama M, Oyama M, Kozuka-Hata H, Hiyoshi M, Kitayama J, Negishi L, Kawasaki Y, Akiyama T (2016) Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1. Proc Natl Acad Sci U S A 113:1273–1278PubMedPubMedCentralCrossRefGoogle Scholar
  115. Taylor JP, Brown RH Jr, Cleveland DW (2016) Decoding ALS: from genes to mechanism. Nature 539:197–206PubMedPubMedCentralCrossRefGoogle Scholar
  116. Ting DT, Lipson D, Paul S, Brannigan BW, Akhavanfard S, Coffman EJ, Contino G, Deshpande V, Iafrate AJ, Letovsky S, Rivera MN, Bardeesy N, Maheswaran S, Haber DA (2011) Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science 331:593–596PubMedPubMedCentralCrossRefGoogle Scholar
  117. Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, König J, Hortobágyi T, Nishimura AL, Zupunski V, Patani R, Chandran S, Rot G, Zupan B, Shaw CE, Ule J (2011) Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci 14:452–458PubMedPubMedCentralCrossRefGoogle Scholar
  118. Tsuiji H, Iguchi Y, Furuya A, Kataoka A, Hatsuta H, Atsuta N, Tanaka F, Hashizume Y, Akatsu H, Murayama S, Sobue G, Yamanaka K (2013) Spliceosome integrity is defective in the motor neuron diseases ALS and SMA. EMBO Mol Med 5:221–234PubMedPubMedCentralCrossRefGoogle Scholar
  119. Tycowski KT, Shu MD, Borah S, Shi M, Steitz JA (2012) Conservation of a triple-helix-forming RNA stability element in noncoding and genomic RNAs of diverse viruses. Cell Rep 2:26–32PubMedPubMedCentralCrossRefGoogle Scholar
  120. Tycowski KT, Shu MD, Steitz JA (2016) Myriad triple-helix-forming structures in the transposable element RNAs of plants and fungi. Cell Rep 15:1266–1276PubMedPubMedCentralCrossRefGoogle Scholar
  121. Ulitsky I, Bartel DP (2013) lincRNAs: genomics, evolution, and mechanisms. Cell 154:26–46PubMedPubMedCentralCrossRefGoogle Scholar
  122. Uversky VN (2016) Intrinsically disordered proteins in overcrowded milieu: membrane-less organelles, phase separation, and intrinsic disorder. Curr Opin Struct Biol 44:18–30PubMedCrossRefGoogle Scholar
  123. Valgardsdottir R, Chiodi I, Giordano M, Rossi A, Bazzini S, Ghigna C, Riva S, Biamonti G (2008) Transcription of Satellite III non-coding RNAs is a general stress response in human cells. Nucleic Acids Res 36:423–434PubMedCrossRefGoogle Scholar
  124. Wahlestedt C (2013) Targeting long non-coding RNA to therapeutically upregulate gene expression. Nat Rev Drug Discov 12:433–446PubMedCrossRefGoogle Scholar
  125. West JA, Davis CP, Sunwoo H, Simon MD, Sadreyev RI, Wang PI, Tolstorukov MY, Kingston RE (2014) The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites. Mol Cell 55:791–802PubMedPubMedCentralCrossRefGoogle Scholar
  126. West JA, Mito M, Kurosaka S, Takumi T, Tanegashima C, Chujo T, Yanaka K, Kingston RE, Hirose T, Bond C, Fox A, Nakagawa S (2016) Structural, super-resolution microscopy analysis of paraspeckle nuclear body organization. J Cell Biol 214:817–830PubMedPubMedCentralCrossRefGoogle Scholar
  127. Wilusz JE, Freier SM, Spector D (2008) 3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell 135:919–932PubMedPubMedCentralCrossRefGoogle Scholar
  128. Wilusz JE, JnBaptiste CK, Lu LY, Kuhn CD, Joshua-Tor L, Sharp PA (2012) A triple helix stabilizes the 3′ ends of long noncoding RNAs that lack poly(A) tails. Genes Dev 26:2392–2407PubMedPubMedCentralCrossRefGoogle Scholar
  129. Wojciechowska M, Krzyzosiak WJ (2011) Cellular toxicity of expanded RNA repeats: focus on RNA foci. Hum Mol Genet 20:3811–3821PubMedPubMedCentralCrossRefGoogle Scholar
  130. Wu H (2013) Higher-order assemblies in a new paradigm of signal transduction. Cell 153:287–292PubMedPubMedCentralCrossRefGoogle Scholar
  131. Yamazaki T, Hirose T (2015) The building process of the functional paraspeckle with long non-coding RNAs. Front Biosci (Elite Ed) 7:1–41CrossRefGoogle Scholar
  132. Yoon JH, Abdelmohsen K, Kim J, Yang X, Martindale JL, Tominaga-Yamanaka K, White EJ, Orjalo AV, Rinn JL, Kreft SG, Wilson GM, Gorospe M (2013) Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination. Nat Commun 4:2939PubMedPubMedCentralCrossRefGoogle Scholar
  133. Zhang Q, Chen CY, Yedavalli VS, Jeang KT (2013) NEAT1 long noncoding RNA and paraspeckle bodies modulate HIV-1 posttranscriptional expression. MBio 4:e00596–e00512PubMedPubMedCentralCrossRefGoogle Scholar
  134. Zucchelli S, Cotella D, Takahashi H, Carrieri C, Cimatti L, Fasolo F, Jones MH, Sblattero D, Sanges R, Santoro C, Persichetti F, Carninci P, Gustincich S (2015a) SINEUPs: a new class of natural and synthetic antisense long non-coding RNAs that activate translation. RNA Biol 12:771–779PubMedPubMedCentralCrossRefGoogle Scholar
  135. Zucchelli S, Fasolo F, Russo R, Cimatti L, Patrucco L, Takahashi H, Jones MH, Santoro C, Sblattero D, Cotella D, Persichetti F, Carninci P, Gustincich S (2015b) SINEUPs are modular antisense long non-coding RNAs that increase synthesis of target proteins in cells. Front Cell Neurosci 9:174PubMedPubMedCentralCrossRefGoogle Scholar
  136. Zucchelli S, Patrucco L, Persichetti F, Gustincich S, Cotella D (2016) Engineering translation in mammalian cell factories to increase protein yield: the unexpected use of long non-coding SINEUP RNAs. Comput Struct Biotechnol J 14:404–410PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Institute for Genetic MedicineHokkaido UniversitySapporoJapan

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