Alternative Polyadenylation Mediates MicroRNA Regulation of Muscle Stem Cell Function
Open accessAbstract
Pax3, a key myogenic regulator, is transiently expressed during activation of adult muscle stem cells, or satellite cells (SCs), and is also expressed in a subset of quiescent SCs (QSCs), but only in specific muscles. The mechanisms regulating these variations in expression are not well understood. Here we show that Pax3 levels are regulated by miR-206, a miRNA with a previously demonstrated role in myogenic differentiation. In most QSCs and activated SCs, miR-206 expression suppresses Pax3 expression. Paradoxically, QSCs that express high levels of Pax3 also express high levels of miR-206. In these QSCs, Pax3 transcripts are subject to alternative polyadenylation, resulting in transcripts with shorter 3' untranslated regions (3'UTRs) that render them resistant to regulation by miR-206. Similar alternate polyadenylation of the Pax3 transcript also occurs in myogenic progenitors during development. Our findings may reflect a general role of alternative polyadenylation in circumventing miRNA-mediated regulation of stem cell function.
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Stem cell quiescence is controlled at least in part by mechanisms that alter 3' UTR length and thus susceptibility to miRNA regulation.
“the importance of transcript 3′ UTRs as targets for miRNAs suggests that stem cell quiescence is controlled, at least in part, by mechanisms that alter 3′ UTR length and thus the susceptibility to regulation by miRNAs92–95.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [92]
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- Authors
- Boutet, S. C., Cheung, T. H., Quach, N. L., Liu, L., Prescott, S. L., Edalati, A., Iori, K., & Rando, T. A.
- Affiliations
- Stanford Medicine (US)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Rando, Thomas A.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 10
- Issue
- 3
- Pages
- 327-336
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC3306803
- OpenAlex
- W2025909136
- Cited by
- 150
- References
- 46
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 13 · 2020: 11 · 2019: 8 · 2018: 10 · 2017: 15 · 2016: 9 · 2015: 14 · 2014: 16 · 2013: 16 · 2012: 9
- FWCI
- 7.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Institutes of Health (DP1OD000392)
- National Institute on Aging (R37AG023806, R01AG023806, P01AG036695)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR062185, R01AR056849)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- alternative polyadenylation, microRNA regulation, miR-206, Pax3, muscle stem cells, satellite cells, quiescent stem cells, 3' untranslated region, myogenesis, myogenic progenitor cells, stem cell quiescence
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Cloning, Molecular, Embryo, Mammalian, Fluorescent Antibody Technique, Gene Expression Regulation, Humans, Mice, Inbred C57BL, Models, Biological, Stem Cells, Polymerase Chain Reaction, Polyadenylation, Myoblasts, MicroRNAs, Mice, Paired Box Transcription Factors, HEK293 Cells
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