title: 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.
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U964, Université de Strasbourg, Illkirch Cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Ballarino
authors.forename: L
authors.initials: L
authors.lastname: Jobert
authors.forename: D
authors.initials: D
authors.lastname: Dembélé
authors.forename: P
authors.initials: P
authors.lastname: de la Grange
authors.forename: D
authors.initials: D
authors.lastname: Auboeuf
authors.forename: L
authors.initials: L
authors.lastname: Tora
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009447:Neuroblastoma / Q000473:pathology; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology; D034622:RNA Interference; D035381:TATA-Binding Protein Associated Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C524941:MIRN17 microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; C102041:TAF15 protein, human; D035381:TATA-Binding Protein Associated Factors