Aller au contenu. | Aller à la navigation

Outils personnels

Navigation
Vous êtes ici : Accueil / Équipes / Regulation of Genome Architecture and Dynamics of Splicing (ReGArDS) - D. Auboeuf / C. Bourgeois / Publications / TAF15 is important for cellular proliferation and regulates the expression of a subset of cell cycle genes through miRNAs.

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

M Ballarino, L Jobert, D Dembele, P de la Grange, D Auboeuf, and L Tora (2013)

Oncogene, 32(39):4646-55.

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. Byperforming 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 expressionof 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.

 
automatic medline import

Actions sur le document