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

Oncogene. 2013 Sep 26;32(39):4646-55. doi: 10.1038/onc.2012.490. Epub 2012 Nov 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Cell Cycle / physiology*
  • Cell Differentiation
  • Cell Division / physiology*
  • Cell Line, Tumor / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Regulatory Networks
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Neuroblastoma / pathology
  • Neurogenesis
  • Neurons / cytology
  • RNA Interference
  • TATA-Binding Protein Associated Factors / antagonists & inhibitors
  • TATA-Binding Protein Associated Factors / genetics
  • TATA-Binding Protein Associated Factors / physiology*


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • MIRN17 microRNA, human
  • MIRN20a microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • TAF15 protein, human
  • TATA-Binding Protein Associated Factors