Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1
Open accessAbstract
HuR influences gene expression programs and hence cellular phenotypes by binding to hundreds of coding and noncoding linear RNAs. However, whether HuR binds to circular RNAs (circRNAs) and impacts on their function is unknown. Here, we have identified en masse circRNAs binding HuR in human cervical carcinoma HeLa cells. One of the most prominent HuR target circRNAs was hsa_circ_0031288, renamed CircPABPN1 as it arises from the PABPN1 pre-mRNA. Further analysis revealed that HuR did not influence CircPABPN1 abundance; interestingly, however, high levels of CircPABPN1 suppressed HuR binding to PABPN1 mRNA. Evaluation of PABPN1 mRNA polysomes indicated that PABPN1 translation was modulated positively by HuR and hence negatively by CircPABPN1. We propose that the extensive binding of CircPABPN1 to HuR prevents HuR binding to PABPN1 mRNA and lowers PABPN1 translation, providing the first example of competition between a circRNA and its cognate mRNA for an RBP that affects translation.
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circPABPN1 inhibits linear splicing by binding to the HuR protein to reduce HeLa cell proliferation and PABPN1 translation.
“Additionally, circular PABPN1 (circPABPN1) has been reported to inhibit linear splicing by binding to the HuR protein to reduce HeLa cell proliferation and PABPN1 translation [66].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [66]
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- Authors
- Abdelmohsen, K., Panda, A. C., Munk, R., Grammatikakis, I., Dudekula, D. B., De, S., Kim, J., Noh, J. H., Kim, K. M., Martindale, J. L., & Gorospe, M.
- Affiliations
- National Institute on Aging (US)
- Corresponding author
- Abdelmohsen, Kotb
- ORCID
- Venue
- RNA Biology
- Publisher
- Informa UK Limited
- Published
- 2017-02-14
- Volume
- 14
- Issue
- 3
- Pages
- 361-369
- ISSN
- 1547-6286 (ISSN-L)
- 1555-8584
- PMC
- PMC5367248
- OpenAlex
- W2572160591
- Cited by
- 858
- References
- 34
- Citations by year
- 2026: 33 · 2025: 59 · 2024: 93 · 2023: 101 · 2022: 131 · 2021: 167 · 2020: 136 · 2019: 67 · 2018: 54 · 2017: 16
- FWCI
- 30.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- RNA Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- HuR, circular RNA, PABPN1, RNA-binding proteins, translational regulation, polysome association, HeLa cells, cervical cancer, pre-mRNA
- MeSH terms
- ELAV-Like Protein 1, RNA, Circular, Base Sequence, Binding Sites, Gene Expression Regulation, Humans, Models, Biological, Protein Binding, RNA, RNA, Messenger, Protein Biosynthesis, Poly(A)-Binding Protein I, Cell Line, Tumor
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