A dynamic actin-dependent nucleoskeleton and cell identity

J Biochem. 2021 Apr 18;169(3):243-257. doi: 10.1093/jb/mvaa133.

Abstract

Actin is an essential regulator of cellular functions. In the eukaryotic cell nucleus, actin regulates chromatin as a bona fide component of chromatin remodelling complexes, it associates with nuclear RNA polymerases to regulate transcription and is involved in co-transcriptional assembly of nascent RNAs into ribonucleoprotein complexes. Actin dynamics are, therefore, emerging as a major regulatory factor affecting diverse cellular processes. Importantly, the involvement of actin dynamics in nuclear functions is redefining the concept of nucleoskeleton from a rigid scaffold to a dynamic entity that is likely linked to the three-dimensional organization of the nuclear genome. In this review, we discuss how nuclear actin, by regulating chromatin structure through phase separation may contribute to the architecture of the nuclear genome during cell differentiation and facilitate the expression of specific gene programs. We focus specifically on mitochondrial genes and how their dysregulation in the absence of actin raises important questions about the role of cytoskeletal proteins in regulating chromatin structure. The discovery of a novel pool of mitochondrial actin that serves as 'mitoskeleton' to facilitate organization of mtDNA supports a general role for actin in genome architecture and a possible function of distinct actin pools in the communication between nucleus and mitochondria.

Keywords: chromatin and transcription regulation; development and differentiation; genome organization and integrity; mitochondria; nuclear actin.

Publication types

  • Review

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Cell Differentiation
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Chromatin / metabolism*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • DNA-Directed RNA Polymerases / metabolism
  • Gene Expression Regulation
  • Genes, Mitochondrial
  • Genome
  • Humans
  • Nuclear Matrix / genetics
  • Nuclear Matrix / metabolism*
  • Transcription, Genetic

Substances

  • Actins
  • Chromatin
  • Cytoskeletal Proteins
  • DNA-Directed RNA Polymerases