Post-transcriptional gene silencing mediated by microRNAs is controlled by nucleoplasmic Sfpq
Open accessAbstract
There is a growing body of evidence about the presence and the activity of the miRISC in the nucleus of mammalian cells. Here, we show by quantitative proteomic analysis that Ago2 interacts with the nucleoplasmic protein Sfpq in an RNA-dependent fashion. By a combination of HITS-CLIP and transcriptomic analyses, we demonstrate that Sfpq directly controls the miRNA targeting of a subset of binding sites by local binding. Sfpq modulates miRNA targeting in both nucleoplasm and cytoplasm, indicating a nucleoplasmic commitment of Sfpq-target mRNAs that globally influences miRNA modes of action. Mechanistically, Sfpq binds to a sizeable set of long 3'UTRs forming aggregates to optimize miRNA positioning/recruitment at selected binding sites, including let-7a binding to Lin28A 3'UTR. Our results extend the miRNA-mediated post-transcriptional gene silencing into the nucleoplasm and indicate that an Sfpq-dependent strategy for controlling miRNA activity takes place in cells, contributing to the complexity of miRNA-dependent gene expression control.
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Low molecular weight miRISC can interact with mRNAs within the nucleus and induce nuclear mRNA degradation.
“It has been reported that low molecular weight miRISC can interact with mRNAs within the nucleus and induce nuclear mRNA degradation, although the mechanism behind this is unclear (59, 61, 63).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [63]
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Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation
O'Brien, J., Hayder, H., Zayed, Y., & Peng, C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00402 · Cited by 5,287 · see citing works
- Authors
- Bottini, S., Hamouda-Tekaya, N., Mategot, R., Zaragosi, L.-E., Audebert, S., Pisano, S., Grandjean, V., Mauduit, C., Benahmed, M., Barbry, P., Repetto, E., & Trabucchi, M.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Lyon 1 Université (FR)
- ORCID
- Venue
- Nature Communications
- Published
- 2017-10-30
- Volume
- 8
- Issue
- 1
- Pages
- 1189-1189
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5662751
- OpenAlex
- W2766537551
- Cited by
- 89
- References
- 72
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 9 · 2023: 14 · 2022: 16 · 2021: 13 · 2020: 14 · 2019: 6 · 2018: 10
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Update notices
- addendum (2026-04-17)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL AMU (submittedVersion, other-oa)
- HAL (submittedVersion)
- HAL Portal Artxiker (Hindustan Aeronautics Limited (India)) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Infrastructures en Biologie Santé et Agronomie
- Agence Nationale de la Recherche (ANR‐10‐INBS‐09‐03, ANR- 10-INBS-09, ANR‐10‐INBS‐09‐02, ANR-10, 10-INBS-09, ANR-11-LABX-0028)
- Institut National de la Santé et de la Recherche Médicale (ANR-11-LABX-0028-01)
- Canceropôle PACA (ANR-11-LABX-0028-01)
- 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 › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- SFPQ, microRNA-induced silencing complex, post-transcriptional gene silencing, miRNA targeting, nucleoplasm, Argonaute 2, 3' untranslated region, let-7a, LIN28A, HITS-CLIP, microRNA binding sites
- MeSH terms
- RAW 264.7 Cells, PTB-Associated Splicing Factor, Animals, Cell Nucleus, HeLa Cells, Humans, Protein Binding, RNA Processing, Post-Transcriptional, RNA-Binding Proteins, 3' Untranslated Regions, Gene Silencing, Gene Expression Profiling, MicroRNAs, Cell Line, Tumor, Mice, HEK293 Cells, Argonaute Proteins
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