microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells.

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 contri...

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Autores principales:	Traude H Beilharz, David T Humphreys, Jennifer L Clancy, Rolf Thermann, David I K Martin, Matthias W Hentze, Thomas Preiss
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83ced30232c94b3c947cf5af2fba3c4b
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spelling	oai:doaj.org-article:83ced30232c94b3c947cf5af2fba3c4b2021-11-25T06:20:46ZmicroRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells.1932-620310.1371/journal.pone.0006783https://doaj.org/article/83ced30232c94b3c947cf5af2fba3c4b2009-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19710908/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Animal 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.Traude H BeilharzDavid T HumphreysJennifer L ClancyRolf ThermannDavid I K MartinMatthias W HentzeThomas PreissPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 8, p e6783 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Traude H Beilharz David T Humphreys Jennifer L Clancy Rolf Thermann David I K Martin Matthias W Hentze Thomas Preiss microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells.
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 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.
format	article
author	Traude H Beilharz David T Humphreys Jennifer L Clancy Rolf Thermann David I K Martin Matthias W Hentze Thomas Preiss
author_facet	Traude H Beilharz David T Humphreys Jennifer L Clancy Rolf Thermann David I K Martin Matthias W Hentze Thomas Preiss
author_sort	Traude H Beilharz
title	microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells.
title_short	microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells.
title_full	microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells.
title_fullStr	microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells.
title_full_unstemmed	microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells.
title_sort	microrna-mediated messenger rna deadenylation contributes to translational repression in mammalian cells.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/83ced30232c94b3c947cf5af2fba3c4b
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microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells.

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