SUN2 mediates calcium-triggered nuclear actin polymerization to cluster active RNA polymerase II

EMBO Rep. 2024 Nov;25(11):4728-4748. doi: 10.1038/s44319-024-00274-8. Epub 2024 Sep 24.

Abstract

The nucleoskeleton is essential for nuclear architecture as well as genome integrity and gene expression. In addition to lamins, titin or spectrins, dynamic actin filament polymerization has emerged as a potential intranuclear structural element but its functions are less well explored. Here we found that calcium elevations trigger rapid nuclear actin assembly requiring the nuclear membrane protein SUN2 independently of its function as a component of the LINC complex. Instead, SUN2 colocalized and associated with the formin and actin nucleator INF2 in the nuclear envelope in a calcium-regulated manner. Moreover, SUN2 is required for active RNA polymerase II (RNA Pol II) clustering in response to calcium elevations. Thus, our data uncover a SUN2-formin module linking the nuclear envelope to intranuclear actin assembly to promote signal-dependent spatial reorganization of active RNA Pol II.

Keywords: Formin; Nuclear Actin; RNA Pol II Clustering; SUN2.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins* / metabolism
  • Animals
  • Calcium* / metabolism
  • Cell Nucleus / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Nuclear Envelope / metabolism
  • Nuclear Proteins / metabolism
  • Polymerization*
  • RNA Polymerase II* / metabolism

Substances

  • RNA Polymerase II
  • Calcium
  • Actins
  • Membrane Proteins
  • SUN2 protein, human
  • Nuclear Proteins
  • Intracellular Signaling Peptides and Proteins