Home LiteratureArticle Details
PMID: 22422859 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish.

Science (New York, N.Y.) ·Vol. 336 ·No. 6078 ·2012-04-13 ·Pages 233-7

Bazzini AA, Lee MT, Giraldez AJ

Abstract

MicroRNAs regulate gene expression through deadenylation, repression, and messenger RNA (mRNA) decay. However, the contribution of each mechanism in non-steady-state situations remains unclear. We monitored the impact of miR-430 on ribosome occupancy of endogenous mRNAs in wild-type and dicer mutant zebrafish embryos and found that miR-430 reduces the number of ribosomes on target mRNAs before causing mRNA decay. Translational repression occurs before complete deadenylation, and disrupting deadenylation with use of an internal polyadenylate tail did not block target repression. Lastly, we observed that ribosome density along the length of the message remains constant, suggesting that translational repression occurs by reducing the rate of initiation rather than affecting elongation or causing ribosomal drop-off. These results show that miR-430 regulates translation initiation before inducing mRNA decay during zebrafish development.

MeSH Terms
3' Untranslated Regions Animals Embryo, Nonmammalian/metabolism Embryonic Development Gene Expression Regulation, Developmental MicroRNAs/genetics,metabolism Peptide Chain Initiation, Translational Poly A/metabolism Protein Biosynthesis RNA Stability RNA, Messenger/metabolism Ribonuclease III/genetics Ribosomes/metabolism Zebrafish/embryology,genetics,metabolism Zebrafish Proteins/biosynthesis,genetics
Chemicals
3' Untranslated Regions MicroRNAs Mirn430 microRNA, zebrafish RNA, Messenger Zebrafish Proteins Poly A Ribonuclease III
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bazzini Ariel A
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Lee Miler T
Giraldez Antonio J
References (30)
30 references, click to expand
  1. A parsimonious model for gene regulation by miRNAs.
    Science. 2011 Feb 4;331(6017):550-3 PMID: 21292970
  2. Pervasive and cooperative deadenylation of 3'UTRs by embryonic microRNA families.
    Mol Cell. 2010 Nov 24;40(4):558-70 PMID: 21095586
  3. Mammalian microRNAs predominantly act to decrease target mRNA levels.
    Nature. 2010 Aug 12;466(7308):835-40 PMID: 20703300
  4. Translational repression by deadenylases.
    J Biol Chem. 2010 Sep 10;285(37):28506-13 PMID: 20634287
  5. Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation.
    Mol Cell. 2009 Sep 24;35(6):868-80 PMID: 19716330
  6. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation.
    Dev Biol. 1999 Dec 15;216(2):671-80 PMID: 10642801
  7. GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets.
    Mol Cell. 2011 Oct 7;44(1):120-33 PMID: 21981923
  8. Regulation of mRNA translation and stability by microRNAs.
    Annu Rev Biochem. 2010;79:351-79 PMID: 20533884
  9. Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation.
    Nature. 2007 Jun 14;447(7146):875-8 PMID: 17507927
  10. Concordant regulation of translation and mRNA abundance for hundreds of targets of a human microRNA.
    PLoS Biol. 2009 Nov;7(11):e1000238 PMID: 19901979
  11. MicroRNAs direct rapid deadenylation of mRNA.
    Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4034-9 PMID: 16495412
  12. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.
    Nature. 2005 Feb 17;433(7027):769-73 PMID: 15685193
  13. PABP is not essential for microRNA-mediated translational repression and deadenylation in vitro.
    EMBO J. 2011 Nov 25;30(24):4998-5009 PMID: 22117217
  14. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling.
    Science. 2009 Apr 10;324(5924):218-23 PMID: 19213877
  15. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
    Cell. 1993 Dec 3;75(5):843-54 PMID: 8252621
  16. MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F.
    Science. 2007 Sep 21;317(5845):1764-7 PMID: 17656684
  17. MicroRNAs: target recognition and regulatory functions.
    Cell. 2009 Jan 23;136(2):215-33 PMID: 19167326
  18. Gene silencing by microRNAs: contributions of translational repression and mRNA decay.
    Nat Rev Genet. 2011 Feb;12(2):99-110 PMID: 21245828
  19. miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs.
    Nat Struct Mol Biol. 2011 Oct 07;18(11):1218-26 PMID: 21984184
  20. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs.
    Science. 2006 Apr 7;312(5770):75-9 PMID: 16484454
  21. microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells.
    PLoS One. 2009 Aug 27;4(8):e6783 PMID: 19710908
  22. Drosophila miR2 primarily targets the m7GpppN cap structure for translational repression.
    Mol Cell. 2009 Sep 24;35(6):881-8 PMID: 19782035
  23. MicroRNAs regulate brain morphogenesis in zebrafish.
    Science. 2005 May 6;308(5723):833-8 PMID: 15774722
  24. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation.
    Cell. 2005 Aug 26;122(4):553-63 PMID: 16122423
  25. The impact of microRNAs on protein output.
    Nature. 2008 Sep 4;455(7209):64-71 PMID: 18668037
  26. An efficient system for let-7 microRNA and GW182 protein-mediated deadenylation in vitro.
    Methods Mol Biol. 2011;725:207-17 PMID: 21528456
  27. miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT.
    Nat Struct Mol Biol. 2011 Oct 07;18(11):1211-7 PMID: 21984185
  28. Inhibition of translational initiation by Let-7 MicroRNA in human cells.
    Science. 2005 Sep 2;309(5740):1573-6 PMID: 16081698
  29. Differential regulation of germline mRNAs in soma and germ cells by zebrafish miR-430.
    Curr Biol. 2006 Nov 7;16(21):2135-42 PMID: 17084698
  30. Deadenylation is a widespread effect of miRNA regulation.
    RNA. 2009 Jan;15(1):21-32 PMID: 19029310
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1215704
Published
2012-04-13
Epub
2012-00-15
Pages
233-7
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3547538
Subset
IM
Grants
NICHD NIH HHS · F32 HD071697 · United States
NIGMS NIH HHS · R01 GM081602 · United States
NIGMS NIH HHS · R01 GM102251 · United States
NIGMS NIH HHS · R01GM081602-05 · United States
Databases
GEO
GSE34743
Corrections
CommentIn
PMID: 22552258
CommentIn
PMID: 22552328
External Links
PubMed source DOI: 10.1126/science.1215704 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2