Zcchc11 Uridylates Mature miRNAs to Enhance Neonatal IGF-1 Expression, Growth, and Survival

English version České info

The Zcchc11 enzyme is implicated in microRNA (miRNA) regulation. It can uridylate let-7 precursors to decrease quantities of the mature miRNA in embryonic stem cell lines, suggested to mediate stem cell maintenance. It can uridylate mature miR-26 to relieve silencing activity without impacting miRNA content in cancer cell lines, suggested to mediate cytokine and growth factor expression. Broader roles of Zcchc11 in shaping or remodeling the miRNome or in directing biological or physiological processes remain entirely speculative. We generated Zcchc11-deficient mice to address these knowledge gaps. Zcchc11 deficiency had no impact on embryogenesis or fetal development, but it significantly decreased survival and growth immediately following birth, indicating a role for this enzyme in early postnatal fitness. Deep sequencing of small RNAs from neonatal livers revealed roles of this enzyme in miRNA sequence diversity. Zcchc11 deficiency diminished the lengths and terminal uridine frequencies for diverse mature miRNAs, but it had no influence on the quantities of any miRNAs. The expression of IGF-1, a liver-derived protein essential to early growth and survival, was enhanced by Zcchc11 expression in vitro, and miRNA silencing of IGF-1 was alleviated by uridylation events observed to be Zcchc11-dependent in the neonatal liver. In neonatal mice, Zcchc11 deficiency significantly decreased IGF-1 mRNA in the liver and IGF-1 protein in the blood. We conclude that the Zcchc11-mediated terminal uridylation of mature miRNAs is pervasive and physiologically significant, especially important in the neonatal period for fostering IGF-1 expression and enhancing postnatal growth and survival. We propose that the miRNA 3′ terminus is a regulatory node upon which multiple enzymes converge to direct silencing activity and tune gene expression.

Vyšlo v časopise: Zcchc11 Uridylates Mature miRNAs to Enhance Neonatal IGF-1 Expression, Growth, and Survival. PLoS Genet 8(11): e32767. doi:10.1371/journal.pgen.1003105
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003105

Souhrn

Zdroje

1. RisslandOS, MikulasovaA, NorburyCJ (2007) Efficient RNA polyuridylation by noncanonical poly(A) polymerases. Mol Cell Biol 27: 3612–3624.

2. KwakJE, WickensM (2007) A family of poly(U) polymerases. RNA 13: 860–867.

3. JonesMR, QuintonLJ, BlahnaMT, NeilsonJR, FuS, et al. (2009) Zcchc11-dependent uridylation of microRNA directs cytokine expression. Nat Cell Biol 11: 1157–1163.

4. KatohT, SakaguchiY, MiyauchiK, SuzukiT, KashiwabaraS, et al. (2009) Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Gene Dev 23: 433–438.

5. BurroughsAM, AndoY, de HoonMJ, TomaruY, NishibuT, et al. (2010) A comprehensive survey of 3′ animal miRNA modification events and a possible role for 3′ adenylation in modulating miRNA targeting effectiveness. Genome Res 20: 1398–1410.

6. HeoI, JooC, KimYK, HaM, YoonMJ, et al. (2009) TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell 138: 696–708.

7. HaganJP, PiskounovaE, GregoryRI (2009) Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells. Nat Struct Mol Biol 16: 1021–1025.

8. HeoI, JooC, ChoJ, HaM, HanJ, et al. (2008) Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. Mol Cell 32: 276–284.

9. ViswanathanSR, DaleyGQ, GregoryRI (2008) Selective Blockade of MicroRNA Processing by Lin28. Science 320: 97–100.

10. StrykeD, KawamotoM, HuangCC, JohnsSJ, KingLA, et al. (2003) BayGenomics: a resource of insertional mutations in mouse embryonic stem cells. Nucleic Acids Res 31: 278–281.

11. PiskounovaE, PolytarchouC, ThorntonJE, LaPierreRJ, PothoulakisC, et al. (2011) Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell 147: 1066–1079.

12. WymanSK, KnoufEC, ParkinRK, FritzBR, LinDW, et al. (2011) Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity. Genome Res 21: 1450–1461.

13. Griffiths-JonesS, SainiHK, van DongenS, EnrightAJ (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36: D154–158.

14. KozomaraA, Griffiths-JonesS (2011) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39: D152–157.

15. LiuJ-P, BakerJ, PerkinsAS, RobertsonEJ, EfstratiadisA (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75: 59–72.

16. BakerJ, LiuJP, RobertsonEJ, EfstratiadisA (1993) Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75: 73–82.

17. TemmermanL, SlonimskyE, RosenthalN (2010) Class 2 IGF-1 isoforms are dispensable for viability, growth and maintenance of IGF-1 serum levels. Growth Horm IGF Res 20: 255–263.

18. BlahnaMT, JonesMR, QuintonLJ, MatsuuraKY, MizgerdJP (2011) Terminal uridyltransferase enzyme Zcchc11 promotes cell proliferation independent of its uridyltransferase activity. J Biol Chem 286: 42381–42389.

19. SchmidtMJ, WestS, NorburyCJ (2011) The human cytoplasmic RNA terminal U-transferase ZCCHC11 targets histone mRNAs for degradation. RNA 17: 39–44.

20. HolzenbergerM, LeneuveP, HamardG, DucosB, PerinL, et al. (2000) A targeted partial invalidation of the insulin-like growth factor I receptor gene in mice causes a postnatal growth deficit. Endocrinology 141: 2557–2566.

21. LemboG, RockmanHA, HunterJJ, SteinmetzH, KochWJ, et al. (1996) Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency. J Clin Invest 98: 2648–2655.

22. ZhuH, ShahS, Shyh-ChangN, ShinodaG, EinhornWS, et al. (2010) Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies. Nat Genet 42: 626–630.

23. YokoyamaS, HashimotoM, ShimizuH, Ueno-KudohH, UchibeK, et al. (2008) Dynamic gene expression of Lin-28 during embryonic development in mouse and chicken. Gene Expr Patterns 8: 155–160.

24. LandgrafP, RusuM, SheridanR, SewerA, IovinoN, et al. (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129: 1401–1414.

25. NakanishiT, KumagaiS, KimuraM, WatanabeH, SakuraiT, et al. (2007) Disruption of mouse poly(A) polymerase mGLD-2 does not alter polyadenylation status in oocytes and somatic cells. Biochem Biophys Res Commun 364: 14–19.

26. MeltonC, JudsonRL, BlellochR (2010) Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature 463: 621–626.

27. ThorntonJE, ChangHM, PiskounovaE, GregoryRI (2012) Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7). RNA 18: 1875–1885.

28. YeomKH, HeoI, LeeJ, HohngS, KimVN, et al. (2011) Single-molecule approach to immunoprecipitated protein complexes: insights into miRNA uridylation. EMBO Rep 12: 690–696.

29. HanBW, HungJH, WengZ, ZamorePD, AmeresSL (2011) The 3′-to-5′ exoribonuclease Nibbler shapes the 3′ ends of microRNAs bound to Drosophila Argonaute1. Curr Biol 21: 1878–1887.

30. LiuN, AbeM, SabinLR, HendriksGJ, NaqviAS, et al. (2011) The exoribonuclease Nibbler controls 3′ end processing of microRNAs in Drosophila. Curr Biol 21: 1888–1893.

31. KimYK, HeoI, KimVN (2010) Modifications of small RNAs and their associated proteins. Cell 143: 703–709.

32. BrockmanW, AlvarezP, YoungS, GarberM, GiannoukosG, et al. (2008) Quality scores and SNP detection in sequencing-by-synthesis systems. Genome Res 18: 763–770.