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Towards a molecular understanding of microRNA-mediated gene silencing
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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“degradation of target mRNA accounts for 66–90% of the miRNA-mediated gene silencing in mammalian cells [84–86]”
From Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability (2025) · cites this paper as [86]
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“In animal cells, the majority of miRNA:MRE interactions are not fully complementary (50).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [50]
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Metadata
- Authors
- Jonas, S., & Izaurralde, E.
- Affiliations
- Max Planck Institute for Developmental Biology (DE)
- Corresponding author
- Izaurralde, Elisa
- Venue
- Nature Reviews Genetics
- Published
- 2015-06-16
- Volume
- 16
- Issue
- 7
- Pages
- 421-433
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- 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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