Molecular functions of nuclear actin in transcription

Abstract

Actin is not only a major cytoskeletal component in all eukaryotic cells but also a nuclear protein that plays a role in gene transcription. We put together data from in vitro and in vivo experiments that begin to provide insights into the molecular mechanisms by which actin functions in transcription. Recent studies performed in vitro have suggested that actin, in direct contact with the transcription apparatus, is required in an early step of transcription that is common to all three eukaryotic RNA polymerases. In addition, there is evidence from in vivo studies that actin is involved in the transcription elongation of class II genes. In this case, actin is bound to a specific subset of premessenger RNA binding proteins, and the actin-messenger RNP complex may constitute a molecular platform for recruitment of histone-modifying enzymes. We discuss a general model for actin in RNA polymerase II transcription whereby actin works as a conformational switch in conjunction with specific adaptors to facilitate the remodeling of large macromolecular assemblies at the promoter and along the active gene.

Figure 1.

Models for the function of actin in chromatin regulation at class II genes. (A) Actin is a component of ATP-dependent chromatin remodeling complexes (CRCs) involved in transcriptional activation. (B) Actin becomes incorporated into the growing pre-mRNP while transcription is taking place. Actin may be recruited directly by hnRNP proteins. An alternative mechanism, supported by the observed binding of actin to the CTD, is that actin is recruited to the transcription machinery via binding to the CTD and subsequently transferred from pol-II to the nascent transcript. Adaptor proteins, such as HRP65-2 in C. tentans and hnRNP U in mammals (see the text for details), help actin recruit HATs that acetylate histones along the gene and maintain the chromatin template in a transcription-competent state. (C) We speculate that actin mediates the cotranscriptional recruitment of chromatin remodeling complexes to active genes through interactions with pol-II and/or with the nascent pre-mRNP.