Poly(A)-binding protein modulates mRNA susceptibility to cap-dependent miRNA-mediated repression
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TLDR
It is reported that both the 5' m(7)G cap and 3' poly(A) tail are essential for maximum miRNA repression and the cis- and trans-acting factors that modulate miRNA efficacy are defined.Abstract:
MicroRNAs (miRNAs) regulate gene expression post-transcriptionally through binding specific sites within the 3' untranslated regions (UTRs) of their target mRNAs. Numerous investigations have documented repressive effects of miRNAs and identified factors required for their activity. However, the precise mechanisms by which miRNAs modulate gene expression are still obscure. Here, we have examined the effects of multiple miRNAs on diverse target transcripts containing artificial or naturally occurring 3' UTRs in human cell culture. In agreement with previous studies, we report that both the 5' m(7)G cap and 3' poly(A) tail are essential for maximum miRNA repression. These cis-acting elements also conferred miRNA susceptibility to target mRNAs translating under the control of viral- and eukaryotic mRNA-derived 5' UTR structures that enable cap-independent translation. Additionally, we evaluated a role for the poly(A)-binding protein (PABP) in miRNA function utilizing multiple approaches to modulate levels of active PABP in cells. PABP expression and activity inversely correlated with the strength of miRNA silencing, in part due to antagonism of target mRNA deadenylation. Together, these findings further define the cis- and trans-acting factors that modulate miRNA efficacy.read more
Citations
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Gene silencing by microRNAs: contributions of translational repression and mRNA decay.
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TL;DR: This work has shown that microRNAs can induce mRNA degradation in animals and, conversely, translational repression in plants and shed light on the specific mechanisms of target silencing.
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Towards a molecular understanding of microRNA-mediated gene silencing
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TL;DR: Understanding of the mechanisms of silencing is enhanced, making it possible to describe in molecular terms a continuum of direct interactions from miRNA target recognition to mRNA deadenylation, decapping and 5′-to-3′ degradation.
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The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC
Marc R. Fabian,Nahum Sonenberg +1 more
TL;DR: Recent discoveries are described, with an emphasis on how miRISC post-transcriptionally controls gene expression by inhibiting translation and/or initiating mRNA decay, and how trans-acting factors control miRNA action.
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The complexity of miRNA-mediated repression.
Anna Wilczynska,Martin Bushell +1 more
TL;DR: The most recent advances in the understanding of the molecular underpinnings of miRNA-mediated repression are discussed and the multitude of regulatory mechanisms that modulate miRNA function are highlighted.
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miRNA-132 orchestrates chromatin remodeling and translational control of the circadian clock
Matías Alvarez-Saavedra,Ghadi Antoun,Akiko Yanagiya,Reynaldo Oliva-Hernandez,Daniel Cornejo-Palma,Carolina Perez-Iratxeta,Nahum Sonenberg,Hai-Ying M. Cheng +7 more
TL;DR: It is proposed that miR-132 is selectively enriched for chromatin- and translation-associated target genes and is an orchestrator of chromatin remodeling and protein translation within the SCN clock, thereby fine-tuning clock entrainment.
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