The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Identification of senescence-associated circular RNAs (SAC-RNAs) reveals senescence suppressor CircPVT1
Open accessAbstract
Using RNA sequencing (RNA-Seq), we compared the expression patterns of circular RNAs in proliferating (early-passage) and senescent (late-passage) human diploid WI-38 fibroblasts. Among the differentially expressed senescence-associated circRNAs (which we termed 'SAC-RNAs'), we identified CircPVT1, generated by circularization of an exon of the PVT1 gene, as a circular RNA showing markedly reduced levels in senescent fibroblasts. Reducing CircPVT1 levels in proliferating fibroblasts triggered senescence, as determined by a rise in senescence-associated β-galactosidase activity, higher abundance of CDKN1A/P21 and TP53, and reduced cell proliferation. Although several microRNAs were predicted to bind CircPVT1, only let-7 was found enriched after pulldown of endogenous CircPVT1, suggesting that CircPVT1 might selectively modulate let-7 activity and hence expression of let-7-regulated mRNAs. Reporter analysis revealed that CircPVT1 decreased the cellular pool of available let-7, and antagonizing endogenous let-7 triggered cell proliferation. Importantly, silencing CircPVT1 promoted cell senescence and reversed the proliferative phenotype observed after let-7 function was impaired. Consequently, the levels of several proliferative proteins that prevent senescence, such as IGF2BP1, KRAS and HMGA2, encoded by let-7 target mRNAs, were reduced by silencing CircPVT1. Our findings indicate that the SAC-RNA CircPVT1, elevated in dividing cells and reduced in senescent cells, sequesters let-7 to enable a proliferative phenotype.
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Circular RNAs are a large class of animal RNAs with regulatory potency
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Cited by
The Biogenesis, Functions, and Challenges of Circular RNAs
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Cytoplasmic functions of long noncoding RNAs
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Self-citationCircular RNAs (circRNAs) in cancer
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Metadata
- Authors
- Panda, A. C., Grammatikakis, I., Kim, K. M., De, S., Martindale, J. L., Munk, R., Yang, X., Abdelmohsen, K., & Gorospe, M.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-12-07
- Volume
- 45
- Issue
- 7
- Pages
- 4021-4035
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2573032256
- Cited by
- 252
- References
- 16
- FWCI
- 12.04
- Type
- journal article
- Language
- en
- Open access
- gold
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- Panda, A. C., Grammatikakis, I., Kim, K. M., De, S., Martindale, J. L., Munk, R., Yang, X., Abdelmohsen, K., & Gorospe, M. (2017). Identification of senescence-associated circular RNAs (SAC-RNAs) reveals senescence suppressor CircPVT1. Nucleic Acids Research. https://doi.org/10.1093/nar/gkw1201
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