Publication:20220117133410
From Bioinformatics Core Wiki
| Publication | |
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| URL | https://pubmed.ncbi.nlm.nih.gov/35021076/ |
| Title | Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1
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| Authors | Rosario Avolio, Marta Inglés-Ferrándiz, Annagiulia Ciocia, Olga Coll, Sarah Bonnin, Tanit Guitart, Anna Ribó, Fátima Gebauer |
| Date | 2022-01-11
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| Publisher | Cell Reports |
| DOI | 10.1016/j.celrep.2021.110211 |
| Tag | Animals, Cell Cycle Checkpoints, Cell Line, Cell Proliferation, Cellular Senescence, DNA-Binding Proteins, Female, Gene Expression, Gene Expression Regulation, Humans, Keratinocytes, Male, Mice, Mice, Inbred C57BL, Mice, Nude, Oncogenes, Primary Cell Culture, RNA Processing, Post-Transcriptional, RNA-Binding Proteins, Senescence-Associated Secretory Phenotype, Signal Transduction, Y-Box-Binding Protein 1, CSDE1, H-Ras(V12), SASP, UNR, YBX1, mRNA stability, oncogene-induced senescence, post-transcriptional regulation, primary mouse keratinocytes, translational control |
Abstract:
Oncogene-induced senescence (OIS) is a form of stable cell-cycle arrest arising in response to oncogenic stimulation. OIS must be bypassed for transformation, but the mechanisms of OIS establishment and bypass remain poorly understood, especially at the post-transcriptional level. Here, we show that the RNA-binding protein UNR/CSDE1 enables OIS in primary mouse keratinocytes. Depletion of CSDE1 leads to senescence bypass, cell immortalization, and tumor formation, indicating that CSDE1 behaves as a tumor suppressor. Unbiased high-throughput analyses uncovered that CSDE1 promotes OIS by two independent molecular mechanisms: enhancement of the stability of senescence-associated secretory phenotype (SASP) factor mRNAs and repression of Ybx1 mRNA translation. Importantly, depletion of YBX1 from immortal keratinocytes rescues senescence and uncouples proliferation arrest from the SASP, revealing multilayered mechanisms exerted by CSDE1 to coordinate senescence. Our data highlight the relevance of post-transcriptional control in the regulation of senescence.
Oncogene-induced senescence (OIS) is a form of stable cell-cycle arrest arising in response to oncogenic stimulation. OIS must be bypassed for transformation, but the mechanisms of OIS establishment and bypass remain poorly understood, especially at the post-transcriptional level. Here, we show that the RNA-binding protein UNR/CSDE1 enables OIS in primary mouse keratinocytes. Depletion of CSDE1 leads to senescence bypass, cell immortalization, and tumor formation, indicating that CSDE1 behaves as a tumor suppressor. Unbiased high-throughput analyses uncovered that CSDE1 promotes OIS by two independent molecular mechanisms: enhancement of the stability of senescence-associated secretory phenotype (SASP) factor mRNAs and repression of Ybx1 mRNA translation. Importantly, depletion of YBX1 from immortal keratinocytes rescues senescence and uncouples proliferation arrest from the SASP, revealing multilayered mechanisms exerted by CSDE1 to coordinate senescence. Our data highlight the relevance of post-transcriptional control in the regulation of senescence.
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