MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies
Open accessAbstract
Small RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs) can silence target genes through several different effector mechanisms. Whereas siRNA-directed mRNA cleavage is increasingly understood, the mechanisms by which miRNAs repress protein synthesis are obscure. Recent studies have revealed the existence of specific cytoplasmic foci, referred to herein as processing bodies (P-bodies), which contain untranslated mRNAs and can serve as sites of mRNA degradation. Here we demonstrate that Argonaute proteins--the signature components of the RNA interference (RNAi) effector complex, RISC--localize to mammalian P-bodies. Moreover, reporter mRNAs that are targeted for translational repression by endogenous or exogenous miRNAs become concentrated in P-bodies in a miRNA-dependent manner. These results provide a link between miRNA function and mammalian P-bodies and suggest that translation repression by RISC delivers mRNAs to P-bodies, either as a cause or as a consequence of inhibiting protein synthesis.
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P-bodies are cytoplasmic foci depleted of ribosomes and enriched with enzymatic mRNA degradation machinery such as mRNA decapping proteins, the CCR4-NOT complex, XRN1, and GW182 family proteins.
“They are cytoplasmic foci depleted of ribosomes (79) and enriched with enzymatic mRNA degradation machinery, such as mRNA decapping proteins, the CCR4-NOT complex, XRN1, and GW182 family proteins (78).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [78]
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- Authors
- Liu, J., Valencia-Sanchez, M. A., Hannon, G. J., & Parker, R.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Hannon, Gregory J.
- Parker, Roy
- Venue
- Nature Cell Biology
- Published
- 2005-06-05
- Volume
- 7
- Issue
- 7
- Pages
- 719-723
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC1855297
- OpenAlex
- W1993180746
- Cited by
- 1,234
- References
- 31
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 19 · 2023: 23 · 2022: 29 · 2021: 39 · 2020: 34 · 2019: 39 · 2018: 48 · 2017: 33 · 2016: 41 · 2015: 52 · 2014: 44 · 2013: 61 · 2012: 89
- FWCI
- 45.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Leukemia and Lymphoma Society
- Cold Spring Harbor Laboratory
- National Institutes of Health
- National Institute of General Medical Sciences (R37GM045443)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- microRNA, P-bodies, Argonaute proteins, RNA-induced silencing complex, protein synthesis inhibition, mRNA localization, mRNA degradation, RNA interference, siRNA, post-transcriptional gene silencing
- MeSH terms
- Cell Line, Endoribonucleases, Gene Expression Regulation, HeLa Cells, Humans, Microscopy, Fluorescence, Mutation, Peptide Initiation Factors, Protein Binding, RNA, Messenger, Transfection, Trans-Activators, Eukaryotic Initiation Factor-2, Receptors, CXCR4, 3' Untranslated Regions, Cytoplasmic Structures, Caenorhabditis elegans Proteins, RNA Transport, RNA, Small Interfering, RNA-Induced Silencing Complex, MicroRNAs, Cell Line, Tumor, Immunoprecipitation, Argonaute Proteins
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