Journal ArticleDOI
MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F
Géraldine Mathonnet,Marc R. Fabian,Yuri V. Svitkin,Armen Parsyan,Laurent Huck,Takayuki Murata,Stefano Biffo,William C. Merrick,Edward Darzynkiewicz,Ramesh S. Pillai,Witold Filipowicz,Thomas F. Duchaine,Nahum Sonenberg +12 more
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TLDR
It is shown here that translation initiation, specifically the 5′ cap recognition process, is repressed by endogenous let-7 miRNAs within the first 15 minutes of mRNA exposure to the extract when no destabilization of the transcript is observed.Abstract:
MicroRNAs (miRNAs) play an important role in gene regulatory networks in animals. Yet, the mechanistic details of their function in translation inhibition or messenger RNA (mRNA) destabilization remain controversial. To directly examine the earliest events in this process, we have developed an in vitro translation system using mouse Krebs-2 ascites cell-free extract that exhibits an authentic miRNA response. We show here that translation initiation, specifically the 5' cap recognition process, is repressed by endogenous let-7 miRNAs within the first 15 minutes of mRNA exposure to the extract when no destabilization of the transcript is observed. Our results indicate that inhibition of translation initiation is the earliest molecular event effected by miRNAs. Other mechanisms, such as mRNA degradation, may subsequently consolidate mRNA silencing.read more
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Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
TL;DR: This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of micro RNA function.
Journal ArticleDOI
Origins and Mechanisms of miRNAs and siRNAs
TL;DR: This work has revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access, which has direct implications for fundamental biology as well as disease etiology and treatment.
Journal ArticleDOI
Widespread changes in protein synthesis induced by microRNAs
Matthias Selbach,Björn Schwanhäusser,Nadine Thierfelder,Zhuo Fang,Raya Khanin,Nikolaus Rajewsky +5 more
TL;DR: It is shown that a single miRNA can repress the production of hundreds of proteins, but that this repression is typically relatively mild, and the data suggest that a mi RNA can, by direct or indirect effects, tune protein synthesis from thousands of genes.
Journal ArticleDOI
Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets
TL;DR: Recent advances in understanding of the molecular structures and biochemical functions of the translation initiation machinery are described and key strategies that mediate general or gene-specific translational control are summarized, particularly in mammalian systems.
Journal ArticleDOI
Regulation of mRNA Translation and Stability by microRNAs
TL;DR: In this article, the authors describe principles of miRNA-mRNA interactions and proteins that interact with miRNAs and function in miRNA mediated repression, and discuss the multiple, often contradictory, mechanisms that miRNA have been reported to use, which cause translational repression and mRNA decay.
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The functions of animal microRNAs
TL;DR: Evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
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MicroRNAs: small RNAs with a big role in gene regulation
Lin He,Gregory J. Hannon +1 more
TL;DR: Two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events and indicate the existence of multiple RISCs that carry out related but specific biological functions.
Journal Article
Oncomirs : microRNAs with a role in cancer
TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
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Oncomirs — microRNAs with a role in cancer
TL;DR: Evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes.
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MicroRNAs Modulate Hematopoietic Lineage Differentiation
TL;DR: The results indicate that microRNAs are components of the molecular circuitry that controls mouse hematopoiesis and suggest that other micro RNAs have similar regulatory roles during other facets of vertebrate development.