Regulating Resilience

  • Patrick L. Iversen


Transcriptome plasticity is an evolutionary surrogate in humans and serves to counter the profound threats imposed by continuously evolving infectious diseases, chemical exposures, and a changing environment. The race to adapt between infections agents and host cells pits very high genome plasticity of viruses and efficient horizontal gene transfer of bacteria against human cell transcriptome plasticity. The human alternate exon use as a “plug and play” strategy creating real time transcriptome plasticity represents a differentiating feature from bacteria and most viruses. Biology always seems to find a way and our resilient transcriptome plasticity can be hacked by infectious agents as they can influence alternate exon use in their host cells as part of their remarkable ability to manipulate their host.

Evolution operates through natural selection. In the case of infectious disease, the human host responds to defend against the infection, most frequently by an immune response. The response imposes natural selection on the infectious pathogen that evolves to evade the host response. Infectious pathogens are at a significant evolutionary advantage due to their relatively short replication interval. If a single-stranded RNA virus is capable of doubling every 10 min then entirely new populations can arise to evade selection pressure in an hour. If bacteria can double every 60 min then an entirely new bacterial population can arise to evade selection pressure within an average workday. Human evolution is much slower such that a generation time of 20 years means a human population can arise to evade selection pressure only after a 100 years or more. An evolutionary competition between humans and their infectious pathogens favors the infectious pathogen and numerous pandemics support this observation.


Splice-site affinity Nuclear receptors Transcription factors Small nuclear ribonucleoproteins Resilient metabolism Placebo effect Aromatherapy 


  1. Ameur A, Zaghlool A, Halvardson J, Wetterbom A, Gyllensten U, Cavelier L, Feuk L. Total RNA sequencing reveals nascent transcription and widespread co-transcriptional splicing in human brain. Nat Struct Mol Biol. 2011;18:1435–40.CrossRefGoogle Scholar
  2. Annalora AJ, Marcus CB, Iversen PL. Alternative splicing in the cytochrome P450 superfamily expands protein diversity to augment gene function and redirect human drug metabolism. Drug Metab Dispos. 2017;45(4):375–89.CrossRefGoogle Scholar
  3. Apostolatos H, Apostolatos A, Vickers T, Watson JE, Song S, Vale F, Cooper DR, Sanchez-Ramos J, Patel NA. Vitamin A metabolite, all-trans-retinoic acid, mediates alternative splicing of protein kinase C deltaVIII (PKCdeltaVIII) isoform via splicing factor SC35. J Biol Chem. 2010;285:25987–95.CrossRefGoogle Scholar
  4. Ashwal-Fluss R, Meyer M, Pamudurti NR, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014;56:55–66.CrossRefGoogle Scholar
  5. Auboeuf D, Honig A, Berget SM, O’Malley BW. Coordinate regulation of transcription and splicing by steroid receptor coregulators. Science. 2002;298:416–9.CrossRefGoogle Scholar
  6. Auboeuf D, Dowhan DH, Dutertre M, Martin N, Berget SM, O’Malley BW. A subset of nuclear receptor coregulators act as coupling proteins during synthesis and maturation of RNA transcripts. Mol Cell Biol. 2005;25:5307–16.CrossRefGoogle Scholar
  7. Ayala R, Shu T, Tsai L-H. Trekking across the brain: the journey of neuronal migration. Cell. 2007;128:29–43.CrossRefGoogle Scholar
  8. Bajgar A, Kucerova K, Jonatova L, Tomcala A, Schneedorferova I, Okrouhlik J, Dolezal T. Extracellular adenosine mediates a systemic metabolic switch during immune response. PLoS Biol. 2015;13(4):e1002135. Scholar
  9. Baumann L, Vujevich J, Halem M, Martin LK, Kerdel F, Lazarus M, Pacheco H, Black L, Bryde J. Open-label pilot study of alitretinoin gel 0.1% in the treatment of photoaging. Cutis. 2005;76:69–73. PubMed: 16144296PubMedGoogle Scholar
  10. Bauren G, Wieslander L. Splicing of Balbiani ring 1 gene pre-mRNA occurs simultaneously with transcription. Cell. 1994;76:183–92.CrossRefGoogle Scholar
  11. Berget SM, Moore C, Sharp PA. Spliced segments at the 5’terminus of adenoirus 2 late mRNA. Proc Natl Acad Sci U S A. 1977;74:3171–5.CrossRefGoogle Scholar
  12. Beverly PC, Daser A, Michie CA, Wallace DL. Functional subsets of T cells defined by isoforms of CD45. Biochem Soc Trans. 1992;20:184–7.CrossRefGoogle Scholar
  13. Bjorklund SS, Panda A, Kumar S, Seiler M, Robinson D, Gheeya J, Yao M, Alnaes GIG, Toppmeyer D, Riis M, Naume B, Borresen-Dale AL, Kristensen VN, Ganesan S, Bhanor G. Widespread alternative exon usage in clinically distinct subtypes of invasive ductal cancinoma. Sci Rep. 2017;7:5568. Scholar
  14. Bolliger MF, Pei J, Maxeiner S, Boucard AA, Grishin NV, Sudhof TC. Unusually rapid evolution of Neuroligin-4 in mice. Proc Natl Acad Sci U S A. 2008;105:6421–6.CrossRefGoogle Scholar
  15. Brunnberg S, Andersson P, Lindstam M, Paulson I, Poellinger L, Hanberg A. The constitutively active Ah receptor (CA-Ahr) mouse as a potential model for dioxin exposure—effects in vital organs. Toxicology. 2006;224:191–201.CrossRefGoogle Scholar
  16. Butcher SE, Brow DA. Towards understanding the catalytic core structure of the spliceosome. Biochem Soc Trans. 2005;33:447–9.CrossRefGoogle Scholar
  17. Carpenter S, Ricci EP, Mercier BC, et al. Post-transcriptional regulation of gene expression in innate immunity. Nat Rev Immunol. 2014;14:361–76.CrossRefGoogle Scholar
  18. Chabot B, Shkreta L. Defective control of pre-messenger RNA splicing in human disease. J Cell Biol. 2016;212:13–27.CrossRefGoogle Scholar
  19. Chow LT, Gelinas RE, Broker TR, Roberts RJ. An amazing sequence arrangement at the 5′-ends of adenovirus 2 messenger RNA. Cell. 1977;12:1–8.CrossRefGoogle Scholar
  20. Christov KT, Moon RC, Lantvit DD, Boone CW, Steele VE, Lubet RA, Kelloff GJ, Pezzuto JM. 9- cis-retinoic acid but not 4-(hydroxyphenyl)retinamide inhibits prostate intraepithelial neoplasia in Noble rats. Cancer Res. 2002;62:5178–82. PubMed: 12234981PubMedGoogle Scholar
  21. Coelho MB, Smith CWJ. Regulation of alternative pre-mRNA splicing. Methods Mol Biol. 2014;126:55–82.CrossRefGoogle Scholar
  22. Danan-Gotthold M, Guyon C, Giraud M, et al. Extensive RNA editing and splicing increase immune self-representation diversity in medullary thymic epithelial cells. Genome Biol. 2016;17:219.CrossRefGoogle Scholar
  23. Dodds EC, Goldberg L, Lawson W, Robinson R. Estrogenic activity of certain synthetic compounds. Nature. 1938;141:247–8.CrossRefGoogle Scholar
  24. Dutertre M, Sanchez G, Barbier J, Corcos L, Auboeuf D. The emerging role of pre-messenger RNA splicing in stress responses: sending alternative messages and silent messengers. RNA Biol. 2011;8:740–7.CrossRefGoogle Scholar
  25. Early P, Huang H, Davis M, et al. Two mRNAs can be produced from a single immunoglobin mu gene by alternative RNA processing pathways. Cell. 1980;20:313–9.CrossRefGoogle Scholar
  26. Gallinaro H, Lazar E, Jacob M, et al. Small RNAs in HnRNP fibrils and their possible function in splicing. Mol Biol Rep. 1981;7:31–9.CrossRefGoogle Scholar
  27. Gannett PM, Iversen PL, Lawson T. Inhibition of cytochrome P-450IIE1 by Dihydrocapsaicin. Bioorg Chem. 1990;18:185–98.CrossRefGoogle Scholar
  28. Gardiner EM, Esteban LM, Fong C, Allison SJ, Flanagan JL, Kouzmenko AP, Eisman JA. Vitamin D receptor B1 and exon 1d: functional and evolutionary analysis. J Steroid Biochem Mol Biol. 2004;89–90:233–8.CrossRefGoogle Scholar
  29. Gehman LT, et al. The splicing regulator Rbfox2 is required for both cerebellar development and mature motor function. Genes Dev. 2012;26:445–60.CrossRefGoogle Scholar
  30. Gilbert W. Why genes in pieces? Nature. 1978;271:501.CrossRefGoogle Scholar
  31. Goren A, Ram O, Amit M, et al. Comparative analysis identifies exonic splicing regulatory sequences- the complex definition of enhancers and silencers. Mol Cell. 2006;22:769–81.CrossRefGoogle Scholar
  32. Grammer K, Fink B, Neave N. Human pheromones and sexual attraction. Eur J Obstet Gynecol Reprod Biol. 2005;118(2):135–42. Scholar
  33. Gu YZ, Hogenesch JB, Bradfield CA. The PAS superfamily: sensors of environmental and developmental signals. Annu Rev Pharmacol Toxicol. 2000;40:519–61.CrossRefGoogle Scholar
  34. Gueroussov S, Gonatopoulos-Pournatzis T, Rimia M, et al. An alternate splicing event amplifies evolutionary differences between vertebrates. Science. 2015;349:868–73.CrossRefGoogle Scholar
  35. Haince JF, McDonald D, Rodrigue A, Dery U, Masson JY, Hendzel MJ, Poirier GG. PARP1-dependent kinetics of recrtuitment of MRE11 and NBS1 proteins to multiple DNA damage sites. J Biol Chem. 2008;283:1197–208.CrossRefGoogle Scholar
  36. Hamada N, Ito H, Iwamoto I, et al. Role of the cytoplasmic isoform of RBFOX1/A2BP1 in establishing the architecture of the developing cerebral cortex. Mol Autism. 2015;6:56.CrossRefGoogle Scholar
  37. Hankinson O. Single-step selection of clones of a mouse hepatoma line deficient in aryl hydrocarbon hydroxylase. Proc Natl Acad Sci U S A. 1979;76:373–6.CrossRefGoogle Scholar
  38. Harper PA, Giannone JV, Okey AB, Denison MS. In vitro transformation of the human Ah receptor and its binding to a dioxin response element. Mol Pharmacol. 1992;42:603–12.PubMedGoogle Scholar
  39. Haussler MR, Norman AW. Chromosomal receptor for a vitamin D metabolite. Proc Natl Acad Sci U S A. January 1969;62(1):155–62.CrossRefGoogle Scholar
  40. Henry EC, Gasiewicz TA. Agonist but not antagonist ligands induce conformational change in the mouse aryl hydrocarbon receptor as detected by partial proteolysis. Mol Pharmacol. 2003;63:392–400.CrossRefGoogle Scholar
  41. Hetherington-Rauth MC, Ramirez SR. Evolution and diversity of floral scent chemistry in the euglossine bee-pollinated orchid genus Gongora. Ann Bot. 2016;118:135–48.CrossRefGoogle Scholar
  42. Holland C, Schmid M, Zimny-Arndt U, et al. Quantitative phosphoproteomics reveals link between Helicobacter pylori infectons and RNA splicing modulation in host cells. Proteomics. 2016;11:2798–811.CrossRefGoogle Scholar
  43. Huang G, Elferink CJ. Multiple mechanisms are involved in Ah receptor-mediated cell cycle arrest. Mol Pharmacol. 2005;67:88–96.CrossRefGoogle Scholar
  44. Huggins C, Grand LC, Brillantes FP. Mammary cancer induced by a single feeding of polymucular hydrocarbons, and its suppression. Nature. 1961;189:204–7.CrossRefGoogle Scholar
  45. Ingram WM, Goodrich LM, Robey EA, Eisen MB. Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance. PLoS One. 2013;8(9):e75246. Scholar
  46. Ivanov A, Memczak S, Wyler E, et al. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep. 2015;10:170–7.CrossRefGoogle Scholar
  47. Jurutka PW, Remus LS, Whitfield GK, Thompson PD, Hsieh JC, Zitzer H, Tavakkoli P, Galligan MA, Dang HT, Haussler CA, Haussler MR. The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor IIB. Mol Endocrinol. 2000;14:401–20.CrossRefGoogle Scholar
  48. Kalam H, Fontana MF, Kumar D. Alternate splicing of transcripts shape macrophage response to Mycobacterium tuberculosis infection. PLoS Pathog. 2017;13(3):e1006236. Scholar
  49. Keightley DD, Okey AB. Effects of dimethylbenz(a)anthracene and dihydrotestosterone on estradiol-17 beta binding in rat mammary cytosol fraction. Cancer Res. 1973;33:2637–42.PubMedGoogle Scholar
  50. Kenemori Y, Koga Y, Sudo M, et al. Biogenesis of sperm acrosome is regulated by pre-mRNA alternative splicing of Acrbp in the mouse. Proc Natl Acad Sci U S A. 2016;113:E3696–2705.CrossRefGoogle Scholar
  51. Krainer AR, Maniatis T. Multiple factors including the small nuclear ribonucleoproteins U1 and U2 are necessary for pre-mRNA splicing in vitro. Cell. 1985;42:211–6.CrossRefGoogle Scholar
  52. Krainer AR, Conway GC, Kozak D. Purificaton and characterization of pre-mRNA splicing factors SF2 from Hela cells. Genes Dev. 1990;4:1158–71.CrossRefGoogle Scholar
  53. Lahvis GP, Bradfield CA. Ahr null alleles: distinctive or different? Biochem Pharmacol. 1998;56:781–7.CrossRefGoogle Scholar
  54. Lahvis GP, Pyzalski RW, Glover E, Pitot HC, McElwee MK, Bradfield CA. The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse. Mol Pharmacol. 2005;67:714–20.CrossRefGoogle Scholar
  55. Lakhan SE, Sheafer H, Tepper D. The effectiveness of aromatherapy in reducing pain: a systematic review and meta-analysis. Pain Res Treat. 2016;2016:1–13. Scholar
  56. Lee JE, Cooper TA. Pathogenic mechanisms of myotonic dystrophy. Biochem Soc Trans. 2009;37:1281–6.CrossRefGoogle Scholar
  57. Legraverend C, Hannah RR, Eisen HJ, Owens IS, Nebert DW, Hankinson O. Regulatory gene product of the ah locus. Characterization of receptor mutants among mouse hepatoma clones. J Biol Chem. 1982;257:6402–7.PubMedGoogle Scholar
  58. Lenzken SC, Loffreda A, Barabino SM. RNA splicing: a new layer in the DNA damage response. Int J Cell Biol. 2013; Scholar
  59. Lerner MR, Boyle JA, Mount SM, et al. Are snRNPs involved in splicing? Nature. 1980;283:220–4.CrossRefGoogle Scholar
  60. Ling S-C, Polymenidou M, Cleveland DW. Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron. 2013;79:416–38.CrossRefGoogle Scholar
  61. Lonard DM, O’Malley BW. Nuclear receptor coregulators: modulators of pathology and therapeutic targets. Nat Rev Endocrinol. 2012;8:598–604.CrossRefGoogle Scholar
  62. Ma J, Liu Z, Michelotti N, Pitchiaya S, Veerapaneni R, Androsavich JR, Walter NG, Yang W. High-resolution three-dimensional mapping of mRNA export through the nuclear pore. Nat Commun. 2013;4:2414. Scholar
  63. Martinez NM, Lynch KW. Control of alternative splicing in immune responses: many regulators, many predictions, much still to learn. Immunol Rev. 2013;253(1):216–36.CrossRefGoogle Scholar
  64. Matthay KK, Reynolds CP, Seeger RC, Shimada H, Adkins ES, Haas-Kogan D, Gerbing RB, London WB, Villablanca JG. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children’s oncology group study. J Clin Oncol. 2009;27:1007–13. PubMed: 19171716CrossRefGoogle Scholar
  65. Matthews J, Gustafsson JA. Estrogen receptor and aryl hydrocarbon receptor signaling pathways. Nucl Recept Signal. 2006;4:e016.CrossRefGoogle Scholar
  66. McKay SJ, Cooke H. hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn. Nucleic Acids Res. 1992;20:6461–4.CrossRefGoogle Scholar
  67. McMillan BJ, Bradfield CA. The Aryl hydrocarbon receptor is activated by modified low-density lipoprotein. Proc Natl Acad Sci USA. 2007;104:1412–7.CrossRefGoogle Scholar
  68. Meininger I, Isabel M, Griesbach RA, et al. Alternative splicing of MALT1 controls signaling and activation of CD4 T cells. Nat Commun. 2016;7:11292.CrossRefGoogle Scholar
  69. Merkin J, Russell C, Chen P, Burge CB. Evolutionary dynamics of gene and isoform regulation in mammalian tissues. Science. 2012;338:1593–9.CrossRefGoogle Scholar
  70. Miau LH, Chang CJ, Shen BJ, Tsai WH, Lee SC. Identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a repressor of C/EBPbeta-mediated gene activation. J Biol Chem. 1998;273:10784–91.CrossRefGoogle Scholar
  71. Mor A, Suliman S, Ben-Yishay R, Yunger S, Brody Y, Shav-Tal Y. Dynamics of single mRNP nucleoplasmic transport and export through the nuclear pore in living cells. Nat Cell Biol. 2010;12:543–54.CrossRefGoogle Scholar
  72. Naro C, Biellli P, Pagliarini V, Sette C. The interplay between DNA damage response and RNA processing: the unexpected role of splicing factors as gatekeepers of genome stability. Front Genet. 2015;
  73. Nojima T, Oshira-Ideue T, Nakanoya H, et al. Herpesvirus protein ICP27 sitches PMO isoform by altering mRNA splicing. Nucleic Acids Res. 2009;37:6515–27.CrossRefGoogle Scholar
  74. Okey A. An aryl hydrocarbon receptor odyssey to the shores of toxicology: the Deichmann lecture, international congress of toxicology-XI. Tox Sci. 2007;98(1):5–38.CrossRefGoogle Scholar
  75. Okuda J, Toyotome T, Kataoka N, et al. Shiella effector IpaH9.8 binds to a splicing factor U2AF(35) to moeulate host immune responses. Biochem Biophys Res Commun. 2005;333:531–9.CrossRefGoogle Scholar
  76. Pistoni M, Ghigna C, Gabellini D. Alternate splicing and muscular dystrophy. RNA Biol. 2010;7:441–52.CrossRefGoogle Scholar
  77. Pohjanvirta R, Wong JMY, Li W, Harper PA, Tuomisto J, Okey AB. Point mutation in intron sequence causes altered carboxylterminal structure in the aryl hydrocarbon receptor of the most 2,3,7,8-tetrachlorodibenzo-p-dioxin-resistant rat strain. Mol Pharmacol. 1998;54:86–93.CrossRefGoogle Scholar
  78. Poland A, Glover E, Kende AS. Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase. J Biol Chem. 1976;251:4936–46.PubMedGoogle Scholar
  79. Reed R, Maniatis T. Intron sequences involved in lariat formation during pre-mRNA splcing. Cell. 1985;41:95–105.CrossRefGoogle Scholar
  80. Rody E, Abelson J. The “spliceosome”: yeast pre-messenger RNA associates with a 40S complex in a splicing-dependent reaction. Science. 1985;28:963–7.Google Scholar
  81. Rogers J. Two mRNAs with different 3’ ends encode membrane-bound and secreted forms of immunoglobin μ chain. Cell. 1980;20:303–12.CrossRefGoogle Scholar
  82. Rosenfeld MG, Lin CR, Amara SG, et al. Calcitonin mRNA polymorphism: peptide switching associated with alternative RNA splicing events. Proc Natl Acad Sci USA. 1982;79:1717–21.CrossRefGoogle Scholar
  83. Safe S, McDougal A. Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone dependent cancers. Int J Oncol. 2002;20:1123–8.PubMedGoogle Scholar
  84. Silinskas KC, Okey AB. Protection by 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) against mammary tumors and leukemia during prolonged feeding of 7,12-dimethylbenz(a)anthracene to female rats. J Natl Cancer Inst. 1975;55:653–7.CrossRefGoogle Scholar
  85. Stern K, McClintock MK. Regulation of ovulation by human pheromones. Nature. 1998;392(6672):177–9. Scholar
  86. Straub RH, Cutolo M, Buttgereit F, Pongratz G. Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J Intern Med. 2010;267(6):543–60.CrossRefGoogle Scholar
  87. Suckale J, et al. PTBP1 is required for embryonic development before gastrulation. PLoS ONE. 2011;6:e16992.CrossRefGoogle Scholar
  88. Takimoto M, Tomonaga T, Matunis M, Avigan M, Krutzsch H, Dreyfuss G, Levens D. Specific binding of heterogeneous ribonucleoprotein particle protein K to the human c-myc promoter, in vitro. J Biol Chem. 1993;268:18249–58.PubMedGoogle Scholar
  89. Taniguchi H, Gollan L, Scholl FG, Mahadomrongkul V, Dobler E, Limthong N, Peck M, Aoki C, Scheiffele P. Silencing of neuroligin function by postsynaptic neurexins. J Neurosci. 2007;27:2815–24.CrossRefGoogle Scholar
  90. Tian B, Manley JL. Alternative polyadenylation of mRNA precursors. Nat Rev Mol Cell Biol. 2017;18:18–30.CrossRefGoogle Scholar
  91. Traunmuller L, Gomez AM, Nguyen T-M, Scheiffele P. Control of neuronal synapse specification by a highly dedicated alternative splicing program. Science. 2016;352:982–6.CrossRefGoogle Scholar
  92. Ule J, Jernej U, Darnell RB. RNA binding proteins and the regulation of neuronal plasticity. Curr Opin Neurobiol. 2006;16:102–10.CrossRefGoogle Scholar
  93. Venables JP, Koh CS, Froehlich U, Lapointe E, Couture S, Inkel L, Bramard A, Paquet ER, Watier V, Durand M, et al. Multiple and specific mRNA processing targets for the major human hnRNP proteins. Mol Cell Biol. 2008;28:6033–43.CrossRefGoogle Scholar
  94. Warner SC, Finta C, Zaphiropoulos PG. Intergenic transcripts containing a novel human cytochrome P450 2C exon 1 spliced to sequences from the CYP2C9. Mol Biol Evol. 2001;18(10):1841–8.CrossRefGoogle Scholar
  95. Wolf G. The discovery of vitamin D: the contribution of Adolf Windaus. J Nutr. 2004;134(6):1299–302.CrossRefGoogle Scholar
  96. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999;98:115–24.CrossRefGoogle Scholar
  97. Wu K, Kim HT, Rodriquez JL, Munoz-Medellin D, Mohsin SK, Hilsenbeck SG, Lamph WW, Gottardis MM, Shirley MA, Kuhn JG, Green JE, Brown PH. 9-cis-retinoic acid suppresses mammary tumorigenesis in C3(1)-simian virus 40 T antigen-transgenic mice. Clin Cancer Res. 2000;6:3696–704. PubMed: 10999763PubMedGoogle Scholar
  98. Xu J, Fang Y, Qin J, et al. A transcriptomic landscape of HPV16 E6-regulated gene expression and splicing events. FEBS Lett. 2016; Scholar
  99. Xue Y, et al. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell. 2013;152:82–96.CrossRefGoogle Scholar
  100. Zhou R, Park JW, Chun RF, Lisse TS, Garcia AJ, Zavala K, Sea JL, Lu ZX, Xu J, Adams JS, Xing Y, Hewison M. Concerted effects of the heterogenous nuclear ribonucleoprotein C1/C2 to control vitamin D-directed gene transcription and RNA splicing in human bone cells. Nucleic Acid Res. 2016;45(2):606–18.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Patrick L. Iversen
    • 1
  1. 1.LS PharmaOregon State UniversityGrand JctUSA

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