Formin-mediated nuclear actin at androgen receptors promotes transcription

Julian Knerr, Ralf Werner, Carsten Schwan, Hong Wang, Peter Gebhardt, Helga Grötsch, Almuth Caliebe, Malte Spielmann, Paul Martin Holterhus, Robert Grosse*, Nadine C. Hornig*

*Corresponding author for this work
2 Citations (Scopus)

Abstract

Steroid hormone receptors are ligand-binding transcription factors essential for mammalian physiology. The androgen receptor (AR) binds androgens mediating gene expression for sexual, somatic and behavioural functions, and is involved in various conditions including androgen insensitivity syndrome and prostate cancer1. Here we identified functional mutations in the formin and actin nucleator DAAM2 in patients with androgen insensitivity syndrome. DAAM2 was enriched in the nucleus, where its localization correlated with that of the AR to form actin-dependent transcriptional droplets in response to dihydrotestosterone. DAAM2 AR droplets ranged from 0.02 to 0.06 µm3 in size and associated with active RNA polymerase II. DAAM2 polymerized actin directly at the AR to promote droplet coalescence in a highly dynamic manner, and nuclear actin polymerization is required for prostate-specific antigen expression in cancer cells. Our data uncover signal-regulated nuclear actin assembly at a steroid hormone receptor necessary for transcription.

Original languageEnglish
JournalNature
Volume617
Issue number7961
Pages (from-to)616-622
Number of pages7
ISSN0028-0836
DOIs
Publication statusPublished - 18.05.2023

Research Areas and Centers

  • Research Area: Medical Genetics

DFG Research Classification Scheme

  • 205-03 Human Genetics

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