Regulation of RNA-polymerase-II-dependent transcription by N-WASP and its nuclear-binding partners

Nat Cell Biol. 2006 Jul;8(7):756-63. doi: 10.1038/ncb1433. Epub 2006 Jun 11.

Abstract

The presence of actin in the nucleus has been well established, and several studies have implicated nuclear actin in transcriptional regulation. Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is a member of the WASP family of proteins; these proteins function in the cytoplasm as key regulators of cortical actin filament. Interestingly, N-WASP has also been observed in the nucleus. However, a potential nuclear function for N-WASP has not been established. Here, we report the identification of nuclear N-WASP within a large nuclear-protein complex containing PSF-NonO (polypyrimidine-tract-binding-protein-associated splicing factor-non-Pou-domain octamer-binding protein/p54(nrb)), nuclear actin and RNA polymerase II. The PSF-NonO complex is involved in the regulation of many cellular processes, such as transcription, RNA processing, DNA unwinding and repair. We demonstrate that the interaction of N-WASP with the PSF-NonO complex can couple N-WASP with RNA polymerase II to regulate transcription. We also provide evidence that the potential function of N-WASP in promoting polymerization of nuclear actins has an important role in this process. Based on these results, we propose a nuclear function for N-WASP in transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism
  • Actins / biosynthesis*
  • Actins / genetics
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • DNA-Binding Proteins
  • Humans
  • Macromolecular Substances / metabolism
  • Nuclear Matrix-Associated Proteins / genetics
  • Nuclear Matrix-Associated Proteins / metabolism
  • Octamer Transcription Factors / genetics
  • Octamer Transcription Factors / metabolism
  • PTB-Associated Splicing Factor
  • Polymers / metabolism
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Regulatory Elements, Transcriptional / genetics*
  • Transcription, Genetic / genetics*
  • Wiskott-Aldrich Syndrome Protein, Neuronal / genetics
  • Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism*

Substances

  • Actins
  • DNA-Binding Proteins
  • Macromolecular Substances
  • NONO protein, human
  • Nuclear Matrix-Associated Proteins
  • Octamer Transcription Factors
  • PTB-Associated Splicing Factor
  • Polymers
  • RNA, Messenger
  • RNA-Binding Proteins
  • WASL protein, human
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • RNA Polymerase II