Phase-specific RNA accumulation and duplex thermodynamics in multiphase coacervate models for membraneless organelles

Saehyun Choi, McCauley C.O. Meyer, Philip C. Bevilacqua, Christine D. Keating

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Liquid–liquid phase separation has emerged as an important means of intracellular RNA compartmentalization. Some membraneless organelles host two or more compartments serving different putative biochemical roles. The mechanisms for, and functional consequences of, this subcompartmentalization are not yet well understood. Here we show that adjacent phases of decapeptide-based multiphase model membraneless organelles differ markedly in their interactions with RNA. Single- and double-stranded RNAs preferentially accumulate in different phases within the same droplet, and one phase is more destabilizing for RNA duplexes than the other. Single-phase peptide droplets did not capture this behaviour. Phase coexistence introduces new thermodynamic equilibria that alter RNA duplex stability and RNA sorting by hybridization state. These effects require neither biospecific RNA-binding sites nor full-length proteins. As such, they are more general and point to primitive versions of mechanisms operating in extant biology that could aid understanding and enable the design of functional artificial membraneless organelles. [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)1110-1117
Number of pages8
JournalNature Chemistry
Volume14
Issue number10
DOIs
StatePublished - Oct 2022

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Chemical Engineering

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