TAF15 is important for cellular proliferation and regulates the expression of a subset of cell cycle genes through miRNAs.

Abstract : TAF15 (formerly TAFII68) is a member of the FET (FUS, EWS, TAF15) family of RNA- and DNA-binding proteins whose genes are frequently translocated in sarcomas. By performing global gene expression profiling, we found that TAF15 knockdown affects the expression of a large subset of genes, of which a significant percentage is involved in cell cycle and cell death. In agreement, TAF15 depletion had a growth-inhibitory effect and resulted in increased apoptosis. Among the TAF15-regulated genes, targets of microRNAs (miRNAs) generated from the onco-miR-17 locus were overrepresented, with CDKN1A/p21 being the top miRNAs-targeted gene. Interestingly, the levels of onco-miR-17 locus coded miRNAs (miR-17-5p and miR-20a) were decreased upon TAF15 depletion and shown to affect the post-transcriptional regulation of TAF15-dependent genes, such as CDKN1A/p21. Thus, our results demonstrate that TAF15 is required to regulate gene expression of cell cycle regulatory genes post-transcriptionally through a pathway involving miRNAs. The findings that high TAF15 levels are needed for rapid cellular proliferation and that endogenous TAF15 levels decrease during differentiation strongly suggest that TAF15 is a key regulator of maintaining a highly proliferative rate of cellular homeostasis.Oncogene advance online publication, 5 November 2012; doi:10.1038/onc.2012.490.
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https://hal.archives-ouvertes.fr/hal-00853421
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Submitted on : Thursday, August 22, 2013 - 4:08:28 PM
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M. Ballarino, L. Jobert, D. Dembélé, P. de la Grange, D. Auboeuf, et al.. TAF15 is important for cellular proliferation and regulates the expression of a subset of cell cycle genes through miRNAs.. Oncogene, Nature Publishing Group, 2012, epub ahead of print. ⟨10.1038/onc.2012.490⟩. ⟨hal-00853421⟩

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