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J. Biol. Chem., Vol. 282, Issue 10, 7616-7623, March 9, 2007

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A Novel Role of the Actin-nucleating Arp2/3 Complex in the Regulation of RNA Polymerase II-dependent Transcription^*

From the Department of Molecular Medicine, Cornell University, Ithaca, New York 14853

It has been well documented that actin is present in the nucleus and involved in numerous nuclear functions including regulation of transcription. The actin-nucleating Arp2/3 complex is an essential, evolutionarily conserved seven-subunit protein complex that promotes actin cytoskeleton assembly in the cytoplasm upon stimulation by WASP family proteins. Our recent study indicates that the nuclear localized neural Wiskott-Aldrich syndrome protein (N-WASP) can induce de novo actin polymerization in the nucleus, and this function is important for the role of N-WASP in the regulation of RNA polymerase II-dependent transcription. Here, we have presented evidence to show that the Arp2/3 complex is also localized in the nucleus and plays an essential role in mediating nuclear actin polymerization induced by N-WASP. We have also demonstrated that the Arp2/3 complex physically associates with RNA polymerase II and is involved in the RNA polymerase II-dependent transcriptional regulation both in vivo and in vitro. Together, these data provide strong support for the hypothesis that N-WASP and the Arp2/3 complex regulate transcription, at least in part, through the regulation of nuclear actin polymerization in a manner similar to their function in the cytoplasm.

Received for publication, August 9, 2006 , and in revised form, January 9, 2007.

^* This research was supported by National Institutes of Health Grant GM48050 (to J.-L. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Div. of Molecular Medicine and Genetics, Dept. of Internal Medicine, Dept. of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109. Tel.: 734-615-4936; Fax: 734-615-2506; E-mail: jlguan{at}umich.edu.

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