Persistent nuclear actin filaments inhibit transcription by RNA polymerase II

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.

Initiation of DNA replication requires actin dynamics and formin activity

“…For example, cell anchorage and the cytoskeleton are involved in growth factordependent transcription, for example, of cyclin D1 in mammalian cells (Assoian & Zhu, 1997), as well as degradation of the CDK inhibitor CDKN1A (Densham et al, 2009). We and others (Serebryannyy et al, 2016) find that treatments that induce nuclear actin filaments eliminate global transcription. We show here that manipulating nuclear actin also arrests DNA replication in a transcriptionindependent manner.…”

“…The form of nuclear actin remains poorly characterised due to difficulties in staining nuclear actin with phalloidin (Grosse & Vartiainen, ) and the large amounts of actin in the cytoplasm. Polymeric nuclear actin is observed in several pathologies (de Lanerolle, ) and can be induced by various manipulations, including heat shock and DMSO treatment (Sanger et al , ; Iida et al , ); increasing nuclear actin concentrations (Stüven et al , ; Kalendová et al , ); activating nuclear mDia2 (Baarlink et al , ); overexpressing NLS‐tagged IQGAP1 (Johnson et al , ) or supervillin (Serebryannyy et al , ); or knockdown of MICAL‐2 (Lundquist et al , ). In specific settings, like the giant quiescent nuclei of amphibian oocytes, a filamentous actin network has scaffolding functions and links nuclear pore complexes to the nuclear interior (Clark & Rosenbaum, ; Gounon & Karsenti, ; Kiseleva et al , ; Feric & Brangwynne, ).…”

Nuclear α-catenin mediates the DNA damage response via β-catenin and nuclear actin

“…EYFP-NLS-S14C-β-actin localizes to the nucleus and stabilizes actin polymerization, while EYFP-NLS-G13R and -R62D-β-actin localize to the nucleus and resist polymerization (Posern et al, 2002;Serebryannyy et al, 2016b). Wild-type EYFP-β-actin was used as a control.…”

“…Nuclear α-catenin attenuates transcription of WNT pathwayresponsive genes via β-catenin. α-Catenin can also influence general transcription by promoting nuclear actin polymerization, suggesting that α-catenin may antagonize transcription at β-cateninregulated promoters by altering the local organization of nuclear actin (Daugherty et al, 2014;Serebryannyy et al, 2016b).…”

The application of pigment-protein fraction from Nannochloropsis oculata on β-actin response of Cromileptes altivelis infected with viral nervous necrosis

“…A report by Visa and Percipalle (2010) stated that β-actin has an essential role in gene expression as a component of chromatin modification complex. In gene expression, β-actin function was connected to RNA Polymerase I, II, and III (Almuzzaini et al, 2016;Serebryannyy, 2016); Hu et al, 2004). On the contrary, Ye et al (2008) stated that actin polymer deficiency will cause actin inability to bind with polymerase I, thus the transcription process is not supported.…”