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Selective RNA Sequestration Mediated by a Heat-Sensing Disordered Protein Region

Research output: Contribution to journalArticle

  • D Allan Drummond
  • Evgeny Pilipenko
  • Joshua Riback
  • Jamie Scott
  • Alexandra Rojek
  • Bogdan Budnik
  • Edward Wallace
  • Christopher Katanski

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Original languageEnglish
JournalThe FASEB Journal
Issue number1 Supplement
Publication statusPublished - Apr 2015


Heat-shocked eukaryotic cells attenuate protein synthesis, mount a transcriptional response, and assemble proteins and RNAs into dynamic cytosolic granules. The constituents of these granules, the mechanism of their formation, their function, and even the mechanism by which eukaryotic cells sense temperature remain unclear. We have developed quantitative mass spectrometric methods that reveal more than a hundred proteins which reversibly assemble in response to heat in budding yeast. Assembly is in some cases protein-autonomous: we report purified proteins self-assembling in vitro with kinetics matching their in vivo assembly, a process encoded in eukaryote-specific domains, including low-complexity, intrinsically disordered regions (IDRs). We report the thermally induced, IDR-mediated assembly of an RNA-binding protein under physiological conditions that is selective for the type of RNA bound, a phenomenon with potential regulatory consequences. Evolutionary analysis of these domains has been challenging because they align poorly between species, a possible consequence of their unusual functional constraints. We introduce novel methods for analyzing liquid/gel-forming sequences, informed by these constraints, which reveal novel signatures of selection and coevolution between proteins interacting through these domains. Together, our results illuminate a corner of a vast cellular regulatory system based on assembly and disassembly which evolves according to unfamiliar yet sensible rules.

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