Cited by 1,872MicroRNA in disease regulationRNA Interference and Gene DeliveryRNA Research and Splicing

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Towards a molecular understanding of microRNA-mediated gene silencing

Jonas, Stefanie, Izaurralde, Elisa·2015·Nature Reviews Genetics

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Abstract

MicroRNAs (miRNAs) are a conserved class of small non-coding RNAs that assemble with Argonaute proteins into miRNA-induced silencing complexes (miRISCs) to direct post-transcriptional silencing of complementary mRNA targets. Silencing is accomplished through a combination of translational repression and mRNA destabilization, with the latter contributing to most of the steady-state repression in animal cell cultures. Degradation of the mRNA target is initiated by deadenylation, which is followed by decapping and 5'-to-3' exonucleolytic decay. Recent work has enhanced our understanding of the mechanisms of silencing, 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. Furthermore, an intricate interplay between translational repression and mRNA degradation is emerging.

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Authors: Jonas, S., & Izaurralde, E.
Affiliations: Max Planck Institute for Developmental Biology (DE)
Corresponding author: Izaurralde, Elisa
ORCID: Jonas, Stefanie
Izaurralde, Elisa
Venue: Nature Reviews Genetics
Publisher: Springer Science and Business Media LLC
Published: 2015-06-16
Volume: 16
Issue: 7
Pages: 421-433
ISSN: 1471-0056 (ISSN-L)
1471-0064
DOI: 10.1038/nrg3965
OpenAlex: W1744683414
Cited by: 1,872
References: 116
Citations by year: 2026: 91 · 2025: 132 · 2024: 142 · 2023: 191 · 2022: 193 · 2021: 216 · 2020: 192 · 2019: 165 · 2018: 217 · 2017: 198 · 2016: 113 · 2015: 20
FWCI: 17.84
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Genetics (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Gottfried Wilhelm Leibniz Universität Hannover
Max-Planck-Gesellschaft
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords: microRNA, gene silencing, post-transcriptional regulation, miRNA-induced silencing complex, Argonaute proteins, mRNA degradation, protein synthesis inhibition, deadenylation, decapping, miRNA target recognition, small RNA
MeSH terms: Animals, Humans, Protein Biosynthesis, Gene Silencing, RNA Stability, MicroRNAs

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Towards a molecular understanding of microRNA-mediated gene silencing

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