Let-7b/c Enhance the Stability of a Tissue-Specific mRNA during Mammalian Organogenesis as Part of a Feedback Loop Involving KSRP
Gene silencing mediated by either microRNAs (miRNAs) or Adenylate/uridylate-rich elements Mediated mRNA Degradation (AMD) is a powerful way to post-transcriptionally modulate gene expression. We and others have reported that the RNA–binding protein KSRP favors the biogenesis of select miRNAs (including let-7 family) and activates AMD promoting the decay of inherently labile mRNAs. Different layers of interplay between miRNA– and AMD–mediated gene silencing have been proposed in cultured cells, but the relationship between the two pathways in living organisms is still elusive. We conditionally deleted Dicer in mouse pituitary from embryonic day (E) 9.5 through Cre-mediated recombination. In situ hybridization, immunohistochemistry, and quantitative reverse transcriptase–PCR revealed that Dicer is essential for pituitary morphogenesis and correct expression of hormones. Strikingly, αGSU (alpha glycoprotein subunit, common to three pituitary hormones) was absent in Dicer-deleted pituitaries. αGSU mRNA is unstable and its half-life increases during pituitary development. A transcriptome-wide analysis of microdissected E12.5 pituitaries revealed a significant increment of KSRP expression in conditional Dicer-deleted mice. We found that KSRP directly binds to αGSU mRNA, promoting its rapid decay; and, during pituitary development, αGSU expression displays an inverse temporal relationship to KSRP. Further, let-7b/c downregulated KSRP expression, promoting the degradation of its mRNA by directly binding to the 3′UTR. Therefore, we propose a model in which let-7b/c and KSRP operate within a negative feedback loop. Starting from E12.5, KSRP induces the maturation of let-7b/c that, in turn, post-transcriptionally downregulates the expression of KSRP itself. This event leads to stabilization of αGSU mRNA, which ultimately enhances the steady-state expression levels. We have identified a post-transcriptional regulatory network active during mouse pituitary development in which the expression of the hormone αGSU is increased by let7b/c through downregulation of KSRP. Our study unveils a functional crosstalk between miRNA– and AMD–dependent gene regulation during mammalian organogenesis events.
Vyšlo v časopise:
Let-7b/c Enhance the Stability of a Tissue-Specific mRNA during Mammalian Organogenesis as Part of a Feedback Loop Involving KSRP. PLoS Genet 8(7): e32767. doi:10.1371/journal.pgen.1002823
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002823
Souhrn
Gene silencing mediated by either microRNAs (miRNAs) or Adenylate/uridylate-rich elements Mediated mRNA Degradation (AMD) is a powerful way to post-transcriptionally modulate gene expression. We and others have reported that the RNA–binding protein KSRP favors the biogenesis of select miRNAs (including let-7 family) and activates AMD promoting the decay of inherently labile mRNAs. Different layers of interplay between miRNA– and AMD–mediated gene silencing have been proposed in cultured cells, but the relationship between the two pathways in living organisms is still elusive. We conditionally deleted Dicer in mouse pituitary from embryonic day (E) 9.5 through Cre-mediated recombination. In situ hybridization, immunohistochemistry, and quantitative reverse transcriptase–PCR revealed that Dicer is essential for pituitary morphogenesis and correct expression of hormones. Strikingly, αGSU (alpha glycoprotein subunit, common to three pituitary hormones) was absent in Dicer-deleted pituitaries. αGSU mRNA is unstable and its half-life increases during pituitary development. A transcriptome-wide analysis of microdissected E12.5 pituitaries revealed a significant increment of KSRP expression in conditional Dicer-deleted mice. We found that KSRP directly binds to αGSU mRNA, promoting its rapid decay; and, during pituitary development, αGSU expression displays an inverse temporal relationship to KSRP. Further, let-7b/c downregulated KSRP expression, promoting the degradation of its mRNA by directly binding to the 3′UTR. Therefore, we propose a model in which let-7b/c and KSRP operate within a negative feedback loop. Starting from E12.5, KSRP induces the maturation of let-7b/c that, in turn, post-transcriptionally downregulates the expression of KSRP itself. This event leads to stabilization of αGSU mRNA, which ultimately enhances the steady-state expression levels. We have identified a post-transcriptional regulatory network active during mouse pituitary development in which the expression of the hormone αGSU is increased by let7b/c through downregulation of KSRP. Our study unveils a functional crosstalk between miRNA– and AMD–dependent gene regulation during mammalian organogenesis events.
Zdroje
1. FabianMRSonenbergNFilipowiczW 2010 Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79 351 379
2. FaraziTASpitzerJIMorozovPTuschlT 2011 miRNAs in human cancer. J Pathol 223 102 115
3. KrolJLoedigeIFilipowiczW 2010 The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11 597 610
4. YamashitaAChangTCYamashitaYZhuWZhongZ 2005 Concerted action of poly(A) nucleases and decapping enzyme in mammalian mRNA turnover. Nat Struct Mol Biol 12 1054 1063
5. von RoretzCDi MarcoSMazrouiRGallouziIE 2011 Turnover of AU-rich-containing mRNAs during stress: a matter of survival. Wiley Interdiscip Rev RNA 2 336 347
6. AbdelmohsenKSrikantanSKuwanoYGorospeM 2008 miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels. Proc Natl Acad Sci U S A 105 20297 20302
7. BhattacharyyaSNHabermacherRMartineUClossEIFilipowiczW 2006 Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 125 1111 1124
8. GuoXWuYHartleyRS 2009 MicroRNA-125a represses cell growth by targeting HuR in breast cancer. RNA Biol 6 575 583
9. JingQHuangSGuthSZarubinTMotoyamaA 2005 Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 120 623 634
10. BriataPChenCYGiovarelliMPaseroMTrabucchiM 2011 KSRP, many functions for a single protein. Front Biosci 16 1787 1796
11. LinWJZhengXLinCCTsaoJZhuX 2011 Posttranscriptional control of type I interferon genes by KSRP in the innate immune response against viral infection. Mol Cell Biol 31 3196 3207
12. ZhangXWanGBergerFGHeXLuX 2011 The ATM Kinase Induces MicroRNA Biogenesis in the DNA Damage Response. Mol Cell 41 371 383
13. ScullyKMRosenfeldMG 2002 Pituitary development: regulatory codes in mammalian organogenesis. Science 295 2231 2235
14. ZhuXGleibermanASRosenfeldMG 2007 Molecular physiology of pituitary development: signaling and transcriptional networks. Physiol Rev 87 933 963
15. BernsteinEKimSYCarmellMAMurchisonEPAlcornH 2003 Dicer is essential for mouse development. Nat Genet 35 215 217
16. HarfeBDMcManusMTMansfieldJHHornsteinETabinCJ 2005 The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A 102 10898 10903
17. OlsonLETollkuhnJScafoglioCKronesAZhangJ 2006 Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination. Cell 125 593 605
18. HarrisKSZhangZMcManusMTHarfeBDSunX 2006 Dicer function is essential for lung epithelium morphogenesis. Proc Natl Acad Sci U S A 103 2208 2213
19. O'RourkeJRGeorgesSASeayHRTapscottSJMcManusMT 2007 Essential role for Dicer during skeletal muscle development. Dev Biol 311 359 368
20. CuellarTLDavisTHNelsonPTLoebGBHarfeBD 2008 Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration. Proc Natl Acad Sci U S A 105 5614 5619
21. JaponMARubinsteinMLowMJ 1994 In situ hybridization analysis of anterior pituitary hormone gene expression during fetal mouse development. J Histochem Cytochem 42 1117 1125
22. PopeCMcNeillyJRCouttsSMillarMAndersonRA 2006 Gonadotrope and thyrotrope development in the human and mouse anterior pituitary gland. Dev Biol 297 172 181
23. KendallSKSamuelsonLCSaundersTLWoodRICamperSA 1995 Targeted disruption of the pituitary glycoprotein hormone alpha-subunit produces hypogonadal and hypothyroid mice. Genes Dev 9 2007 2019
24. EgashiraNTakekoshiSTakeiMTeramotoAOsamuraRY 2011 Expression of FOXL2 in human normal pituitaries and pituitary adenomas. Mod Pathol 24 765 773
25. ChedresePJKayTWJamesonJL 1994 Gonadotropin-releasing hormone stimulates glycoprotein hormone alpha-subunit messenger ribonucleic acid (mRNA) levels in alpha T3 cells by increasing transcription and mRNA stability. Endocrinology 134 2475 2481
26. Garcia-MayoralMFDiaz-MorenoIHollingworthDRamosA 2008 The sequence selectivity of KSRP explains its flexibility in the recognition of the RNA targets. Nucleic Acids Res 36 5290 5296
27. GherziRTrabucchiMPonassiMRuggieroTCorteG 2006 The RNA-binding protein KSRP promotes decay of beta-catenin mRNA and is inactivated by PI3K-AKT signaling. PLoS Biol 5 e5 doi:10.1371/journal.pbio.0050005
28. PiskounovaEPolytarchouCThorntonJELaPierreRJPothoulakisC 2011 Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell 147 1066 1079
29. ViswanathanSRDaleyGQGregoryRI 2008 Selective blockade of microRNA processing by Lin28. Science 320 97 100
30. MichlewskiGCaceresJF 2010 Antagonistic role of hnRNP A1 and KSRP in the regulation of let-7a biogenesis. Nat Struct Mol Biol 17 1011 1018
31. RuggieroTTrabucchiMDe SantaFZupoSHarfeBD 2009 LPS induces KH-type splicing regulatory protein-dependent processing of microRNA-155 precursors in macrophages. Faseb J 23 2898 2908
32. TrabucchiMBriataPGarcia-MayoralMHaaseADFilipowiczW 2009 The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 459 1010 1014
33. KimHHKuwanoYSrikantanSLeeEKMartindaleJL 2009 HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev 23 1743 1748
34. MaFLiuXLiDWangPLiN 2010 MicroRNA-466l upregulates IL-10 expression in TLR-triggered macrophages by antagonizing RNA-binding protein Tristetraprolin-mediated IL-10 mRNA degradation. J Immunol 184 6053 6059
35. VasudevanSTangYSteitzJA 2007 Switching from repression to activation: microRNAs can up-regulate translation. Science 318 1931 1934
36. ZhuXZhangJTollkuhnJOhsawaRBresnickEH 2006 Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesis. Genes Dev 20 2739 2753
37. SimonRLamALiMCNganMMenenzesS 2007 Analysis of gene expression data using BRB-ArrayTools. Cancer Inform 3 11 17
38. BriataPIlengoCCorteGMoroniCRosenfeldMG 2003 The Wnt/beta-catenin–>Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs. Mol Cell 12 1201 1211
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 7
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