Persistent nuclear actin filaments inhibit transcription by RNA polymerase II.

Leonid A Serebryannyy,Cara J Gottardi,Christina M Cruz,Paolo Annibale,Primal De Lanerolle,Megan Parilla,Kyle Laster,Dmitri Kudryashov,Steven T Kosak,Enrico Gratton

doi:10.1242/jcs.195867

Abstract

Actin is abundant in the nucleus and it is clear that nuclear actin has important functions. However, mystery surrounds the absence of classical actin filaments in the nucleus. To address this question, we investigated how polymerizing nuclear actin into persistent nuclear actin filaments affected transcription by RNA polymerase II. Nuclear filaments impaired nuclear actin dynamics by polymerizing and sequestering nuclear actin. Polymerizing actin into stable nuclear filaments disrupted the interaction of actin with RNA polymerase II and correlated with impaired RNA polymerase II localization, dynamics, gene recruitment, and reduced global transcription and cell proliferation. Polymerizing and crosslinking nuclear actin in vitro similarly disrupted the actin-RNA-polymerase-II interaction and inhibited transcription. These data rationalize the general absence of stable actin filaments in mammalian somatic nuclei. They also suggest a dynamic pool of nuclear actin is required for the proper localization and activity of RNA polymerase II.

Highlights

Actin is one of the most evolutionarily conserved and abundant cellular proteins (Pollard and Cooper, 2009)
Expressing a fragment of supervillin (Fig. 1C) resulted in the polymerization of endogenous actin into stable nuclear actin filaments that can be stained with phalloidin
Taking advantage of an actin mutation that promotes nuclear actin filament formation and disease, along with approaches to induce nuclear actin filaments both in cells and in vitro, we show that forming nuclear actin filaments inhibits transcription by RNA polymerase II (RNAPII)

Summary

Introduction

Actin is one of the most evolutionarily conserved and abundant cellular proteins (Pollard and Cooper, 2009). Actin is found in the nucleus and is integral to many nuclear processes (reviewed in de Lanerolle, 2012; de Lanerolle and Serebryannyy, 2011; Grosse and Vartiainen, 2013). The ability of actin to polymerize and depolymerize, which is crucial for its physiological functions (Pollard and Cooper, 2009), is sensitively regulated. Many of the same regulators of actin polymerization shuttle into the nucleus, suggesting that actin dynamics are key to its nuclear functions (de Lanerolle and Serebryannyy, 2011; Gettemans et al, 2005; Grosse and Vartiainen, 2013)

Methods

Results

Conclusion