UBAP2L contributes to formation of P-bodies and modulates their association with stress granules

J Cell Biol. 2024 Oct 7;223(10):e202307146. doi: 10.1083/jcb.202307146. Epub 2024 Jul 15.

Abstract

Stress triggers the formation of two distinct cytoplasmic biomolecular condensates: stress granules (SGs) and processing bodies (PBs), both of which may contribute to stress-responsive translation regulation. Though PBs can be present constitutively, stress can increase their number and size and lead to their interaction with stress-induced SGs. The mechanism of such interaction, however, is largely unknown. Formation of canonical SGs requires the RNA binding protein Ubiquitin-Associated Protein 2-Like (UBAP2L), which is a central SG node protein in the RNA-protein interaction network of SGs and PBs. UBAP2L binds to the essential SG and PB proteins G3BP and DDX6, respectively. Research on UBAP2L has mostly focused on its role in SGs, but not its connection to PBs. We find that UBAP2L is not solely an SG protein but also localizes to PBs in certain conditions, contributes to PB biogenesis and SG-PB interactions, and can nucleate hybrid granules containing SG and PB components in cells. These findings inform a new model for SG and PB formation in the context of UBAP2L's role.

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cytoplasmic Granules / metabolism
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Processing Bodies / genetics
  • Processing Bodies / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins
  • RNA Helicases* / genetics
  • RNA Helicases* / metabolism
  • RNA Recognition Motif Proteins* / genetics
  • RNA Recognition Motif Proteins* / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Stress Granules* / genetics
  • Stress Granules* / metabolism

Substances

  • Ubap2L protein, human
  • RNA Helicases
  • RNA Recognition Motif Proteins
  • G3BP1 protein, human
  • RNA-Binding Proteins
  • DEAD-box RNA Helicases
  • DDX6 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • DNA Helicases
  • Carrier Proteins
  • Proto-Oncogene Proteins