A DEAD-box helicase drives the partitioning of a pro-differentiation NAB protein into nuclear foci

Nat Commun. 2023 Oct 18;14(1):6593. doi: 10.1038/s41467-023-42345-9.

Abstract

How cells regulate gene expression in a precise spatiotemporal manner during organismal development is a fundamental question in biology. Although the role of transcriptional condensates in gene regulation has been established, little is known about the function and regulation of these molecular assemblies in the context of animal development and physiology. Here we show that the evolutionarily conserved DEAD-box helicase DDX-23 controls cell fate in Caenorhabditis elegans by binding to and facilitating the condensation of MAB-10, the C. elegans homolog of mammalian NGFI-A-binding (NAB) protein. MAB-10 is a transcriptional cofactor that functions with the early growth response (EGR) protein LIN-29 to regulate the transcription of genes required for exiting the cell cycle, terminal differentiation, and the larval-to-adult transition. We suggest that DEAD-box helicase proteins function more generally during animal development to control the condensation of NAB proteins important in cell identity and that this mechanism is evolutionarily conserved. In mammals, such a mechanism might underlie terminal cell differentiation and when dysregulated might promote cancerous growth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Carrier Proteins / metabolism
  • Cell Differentiation / genetics
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • DNA-Binding Proteins* / metabolism
  • Mammals / metabolism

Substances

  • DNA-Binding Proteins
  • Carrier Proteins
  • Caenorhabditis elegans Proteins
  • DEAD-box RNA Helicases