title: Regulation of RNA-polymerase-II-dependent transcription by N-WASP and its nuclear-binding partners.
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.
authors.affiliation: Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wu
authors.forename: Youngdong
authors.initials: Y
authors.lastname: Yoo
authors.forename: Nataly N
authors.initials: NN
authors.lastname: Okuhama
authors.forename: Philip W
authors.initials: PW
authors.lastname: Tucker
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: Guan
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000096:biosynthesis* / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D050810:Octamer Transcription Factors / Q000235:genetics / Q000378:metabolism; D000072670:PTB-Associated Splicing Factor; D011108:Polymers / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D000072670:PTB-Associated Splicing Factor; D011108:Polymers; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C495771:WASL protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D012319:RNA Polymerase II