mRNA recruitment by G3BP1 condensates is regulated by Caprin1 but requires G3BP1 binding to mRNA

Upon stress exposure, cells repress translation and release mRNAs from polysomes. The sudden increase in cytoplasmic messenger RNA (mRNA) concentration triggers the formation of cytoplasmic condensates known as stress granules (SGs) that enrich mRNA and RNA binding proteins (RBPs). SGs assemble through liquid-liquid phase separation involving interactions between a subset of RBPs and mRNA. G3BP1 is considered the central participant of this network and functions as a molecular switch depending on the mRNA concentration and the recruitment of G3BP1 protein partners. Among them, Caprin1 is an SG associated protein that binds the NTF2-L domain of G3BP1, promoting SG assembly. Herein, we show that Caprin1 triggers the formation of large G3BP1-mRNA condensates in vitro and improves both the mRNA and G3BP1 recruitment in SGs. However, this function requires intact RNA binding domains of G3BP1. Additionally, the central intrinsically disordered region (IDR2) of G3BP1 regulates the G3BP1 mRNA binding. However, Caprin1 restores the recruitment in SGs of G3BP1-ΔIDR2. We propose that heterotypic interactions between Caprin1 and G3BP1 contribute to the centrality of G3BP1 by increasing the recruitment of mRNA by G3BP1 which is fundamental for condensate formation.

• Publication year

  2025

• Venue

  Scientific Reports

• Publication date

  2025-10-23

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/s41598-025-21066-7PMID 41131140PMCID 12550004
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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