Intrinsically Disordered Regions Can Contribute Promiscuous Interactions to RNP Granule Assembly

David S.W. Protter, Bhalchandra S. Rao, Briana Van Treeck, Yuan Lin, Laura Mizoue, Michael K. Rosen, Roy Parker

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Eukaryotic cells contain large RNA-protein assemblies referred to as RNP granules, whose assembly is promoted by both traditional protein interactions and intrinsically disordered protein domains. Using RNP granules as an example, we provide evidence for an assembly mechanism of large cellular structures wherein specific protein-protein or protein-RNA interactions act together with promiscuous interactions of intrinsically disordered regions (IDRs). This synergistic assembly mechanism illuminates RNP granule assembly and explains why many components of RNP granules, and other large dynamic assemblies, contain IDRs linked to specific protein-protein or protein-RNA interaction modules. We suggest assemblies based on combinations of specific interactions and promiscuous IDRs are common features of eukaryotic cells. Many RNA-binding proteins contain disordered regions. Protter et al. find that these regions interact nonspecifically with other proteins, which can disrupt phase separation in vitro. They also find that promiscuous interactions synergize with specific interactions to promote phase separation and formation of higher-order structures, like RNP granules.

Original languageEnglish (US)
Pages (from-to)1401-1412
Number of pages12
JournalCell Reports
Volume22
Issue number6
DOIs
Publication statusPublished - Feb 6 2018

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Keywords

  • Dhh1
  • intrinsically disordered
  • P-body
  • phase separation
  • RNP granule

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Protter, D. S. W., Rao, B. S., Van Treeck, B., Lin, Y., Mizoue, L., Rosen, M. K., & Parker, R. (2018). Intrinsically Disordered Regions Can Contribute Promiscuous Interactions to RNP Granule Assembly. Cell Reports, 22(6), 1401-1412. https://doi.org/10.1016/j.celrep.2018.01.036