MicroRNA-mediated mRNA translation activation in quiescent cells and oocytes involves recruitment of a nuclear microRNP
Open accessAbstract
MicroRNAs can promote translation of specific mRNAs in quiescent (G0) mammalian cells and immature Xenopus laevis oocytes. We report that microRNA-mediated upregulation of target mRNAs in oocytes is dependent on nuclear entry of the microRNA; cytoplasmically-injected microRNA repress target mRNAs. Components of the activation microRNP, AGO, FXR1 (FXR1-iso-a) and miR16 are present in the nucleus and cytoplasm. Importantly, microRNA target mRNAs for upregulation, Myt1, TNFα and a reporter bearing the TNFα AU-rich, microRNA target sequence, are associated with AGO in immature oocyte nuclei and AGO2 in G0 human nuclei, respectively. mRNAs that are repressed or lack target sites are not associated with nuclear AGO. Crosslinking-coupled immunopurification revealed greater association of AGO2 with FXR1 in the nucleus compared to cytoplasm. Consistently, overexpression of FXR1-iso-a rescues activation of cytoplasmically-injected RNAs and in low density, proliferating cells. These data indicate the importance of a compartmentalized AGO2-FXR1-iso-a complex for selective recruitment for microRNA-mediated upregulation.
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miRNA-mediated activation of translation involves AGO2 and FXR1 instead of GW182.
“The miRNA-mediated activation of translation involves AGO2 and FXR1 instead of GW182 (56).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [56]
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- Authors
- Truesdell, S. S., Mortensen, R. D., Seo, M., Schroeder, J. C., Lee, J. H., LeTonqueze, O., & Vasudevan, S.
- Affiliations
- Harvard University (US)
- Corresponding author
- Vasudevan, S.
- Venue
- Scientific Reports
- Published
- 2012-11-13
- Volume
- 2
- Issue
- 1
- Pages
- 842-842
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC3496365
- OpenAlex
- W2122142258
- Cited by
- 173
- References
- 60
- Citations by year
- 2026: 3 · 2025: 19 · 2024: 15 · 2023: 16 · 2022: 18 · 2021: 21 · 2020: 14 · 2019: 9 · 2018: 10 · 2017: 10 · 2016: 13 · 2015: 7 · 2014: 10 · 2013: 7 · 2012: 1
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Cancer Research Institute
- Richard and Susan Smith Family Foundation
- Leukemia and Lymphoma Society
- 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, Argonaute 2, FXR1, quiescent cells, G0 phase, oocytes, AU-rich elements, TNF-α, Myt1, protein synthesis inhibition
- MeSH terms
- Animals, Cell Line, Cell Nucleus, Cytoplasm, Humans, Oocytes, Protein-Tyrosine Kinases, RNA, Messenger, Protein Biosynthesis, Xenopus laevis, Up-Regulation, Resting Phase, Cell Cycle, RNA-Binding Proteins, Protein Serine-Threonine Kinases, Xenopus Proteins, MicroRNAs, Argonaute Proteins
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