microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells
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Beilharz, Traude H.; Humphreys, David T.; Clancy, Jennifer L.; Thermann, Rolf; Martin, David I. K.; Hentze, Matthias W.; Preiss, Thomas
Description
Animal microRNAs (miRNAs) typically regulate gene expression by binding to partially complementary target sites in the 3' untranslated region (UTR) of messenger RNA (mRNA) reducing its translation and stability. They also commonly induce shortening of the mRNA 3' poly(A) tail, which contributes to their mRNA decay promoting function. The relationship between miRNA-mediated deadenylation and translational repression has been less clear. Using transfection of reporter constructs carrying three...[Show more]
dc.contributor.author | Beilharz, Traude H. | |
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dc.contributor.author | Humphreys, David T. | |
dc.contributor.author | Clancy, Jennifer L. | |
dc.contributor.author | Thermann, Rolf | |
dc.contributor.author | Martin, David I. K. | |
dc.contributor.author | Hentze, Matthias W. | |
dc.contributor.author | Preiss, Thomas | |
dc.date.accessioned | 2015-10-26T23:04:20Z | |
dc.date.available | 2015-10-26T23:04:20Z | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/1885/16090 | |
dc.description.abstract | Animal microRNAs (miRNAs) typically regulate gene expression by binding to partially complementary target sites in the 3' untranslated region (UTR) of messenger RNA (mRNA) reducing its translation and stability. They also commonly induce shortening of the mRNA 3' poly(A) tail, which contributes to their mRNA decay promoting function. The relationship between miRNA-mediated deadenylation and translational repression has been less clear. Using transfection of reporter constructs carrying three imperfectly matching let-7 target sites in the 3' UTR into mammalian cells we observe rapid target mRNA deadenylation that precedes measureable translational repression by endogenous let-7 miRNA. Depleting cells of the argonaute co-factors RCK or TNRC6A can impair let-7-mediated repression despite ongoing mRNA deadenylation, indicating that deadenylation alone is not sufficient to effect full repression. Nevertheless, the magnitude of translational repression by let-7 is diminished when the target reporter lacks a poly(A) tail. Employing an antisense strategy to block deadenylation of target mRNA with poly(A) tail also partially impairs translational repression. On the one hand, these experiments confirm that tail removal by deadenylation is not strictly required for translational repression. On the other hand they show directly that deadenylation can augment miRNA-mediated translational repression in mammalian cells beyond stimulating mRNA decay. Taken together with published work, these results suggest a dual role of deadenylation in miRNA function: it contributes to translational repression as well as mRNA decay and is thus critically involved in establishing the quantitatively appropriate physiological response to miRNAs. | |
dc.description.sponsorship | This work was funded by grants from the Australian Research Council (DP0878224; http://www.arc.gov.au/), the National Health & Medical Research Council (#573726; http://www.nhmrc.gov.au/), and the Sylvia & Charles Viertel Charitable Foundation (Senior Medical Research Fellowship; http://www.anz.com/ aus/Invest-And-Insure/Product-And-Services/ANZ-Trustees/Apply-For-A-Grant/Named-Charitable-Trusts.asp#Viertel). | |
dc.format | 12 pages | |
dc.publisher | Public Library of Science | |
dc.rights | © 2009 Beilharz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
dc.source | PLoS ONE | |
dc.subject | base sequence | |
dc.subject | dna primers | |
dc.subject | hela cells | |
dc.subject | humans | |
dc.subject | micrornas | |
dc.subject | poly a | |
dc.subject | protein biosynthesis | |
dc.subject | rna, messenger | |
dc.subject | reverse transcriptase polymerase chain reaction | |
dc.title | microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 4 | |
dcterms.dateAccepted | 2009-07-24 | |
dc.date.issued | 2009-08-27 | |
local.identifier.absfor | 060405 | |
local.identifier.absfor | 111203 | |
local.identifier.ariespublication | u4020362xPUB241 | |
local.publisher.url | https://www.plos.org/ | |
local.type.status | Published Version | |
local.contributor.affiliation | Beilharz, Traude H, Victor Chang Cardiac Research Institute, Australia | |
local.contributor.affiliation | Humphreys, David T, Victor Chang Chardiac Research Institute, Australia | |
local.contributor.affiliation | Clancy, Jennifer, Victor Chang Cardiac Research Institute, Australia | |
local.contributor.affiliation | Thermann, Rolf, European Molecular Biology Laboratory, Germany | |
local.contributor.affiliation | Martin, David I K, Children's Hospital Oakland Institute, United States of America | |
local.contributor.affiliation | Hentze, Matthias, EMBL, Germany, Germany | |
local.contributor.affiliation | Preiss, Thomas, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Genome Sciences, The Australian National University | |
dc.relation | http://purl.org/au-research/grants/arc/DP0878224 | |
dc.relation | http://purl.org/au-research/grants/nhmrc/573726 | |
local.identifier.essn | 1932-6203 | |
local.bibliographicCitation.issue | 8 | |
local.bibliographicCitation.startpage | e6783 | |
local.identifier.doi | 10.1371/journal.pone.0006783 | |
dc.date.updated | 2015-12-09T08:53:00Z | |
local.identifier.scopusID | 2-s2.0-69449099275 | |
local.identifier.thomsonID | 000269415600004 | |
Collections | ANU Research Publications |
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