2. Academic Validation
  3. Phospho-dependent phase separation of FMRP and CAPRIN1 recapitulates regulation of translation and deadenylation

Phospho-dependent phase separation of FMRP and CAPRIN1 recapitulates regulation of translation and deadenylation

  • Science. 2019 Aug 23;365(6455):825-829. doi: 10.1126/science.aax4240.
Tae Hun Kim 1 2 3 4,  Brian Tsang 1 2,  Robert M Vernon 1,  Nahum Sonenberg 5 6,  Lewis E Kay 1 2 3 4,  Julie D Forman-Kay 7 2
Affiliations

Affiliations

  • 1 Program in Molecular Medicine, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
  • 2 Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
  • 3 Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
  • 4 Department of Chemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
  • 5 Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada.
  • 6 Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.
  • 7 Program in Molecular Medicine, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada. forman@sickkids.ca.
PMID: 31439799 DOI: 10.1126/science.aax4240
Abstract

Membraneless organelles involved in RNA processing are biomolecular condensates assembled by phase separation. Despite the important role of intrinsically disordered protein regions (IDRs), the specific interactions underlying IDR phase separation and its functional consequences remain elusive. To address these questions, we used minimal condensates formed from the C-terminal disordered regions of two interacting translational regulators, FMRP and CAPRIN1. Nuclear magnetic resonance spectroscopy of FMRP-CAPRIN1 condensates revealed interactions involving arginine-rich and aromatic-rich regions. We found that different FMRP serine/threonine and CAPRIN1 tyrosine phosphorylation patterns control phase separation propensity with RNA, including subcompartmentalization, and tune deadenylation and translation rates in vitro. The resulting evidence for residue-specific interactions underlying co-phase separation, phosphorylation-modulated condensate architecture, and enzymatic activity within condensates has implications for how the integration of signaling pathways controls RNA processing and translation.

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