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

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Abstract
The presence of actin in the nucleus has been well established, and several studies have implicated nuclear actin in transcriptional regulation1,2,3. 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 filament4,5,6. Interestingly, N-WASP has also been observed in the nucleus7,8,9,10,11. 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/p54nrb), nuclear actin and RNA polymerase II. The PSF–NonO complex is involved in the regulation of many cellular processes12, 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.