美国宾夕法尼亚大学Keating Christine D.团队报道了无膜细胞器多相凝聚模型中的相特异性RNA积累和双重热动力学。相关研究成果于2022年6月30日发表于国际顶尖学术期刊《自然—化学》。
液-液相分离已成为细胞内RNA区域化的重要手段。一些无膜细胞器拥有两个或多个小室，发挥着不同的假定生化作用。这种分割机制和功能后果尚不清楚。
该文中，研究人员表明，基于十肽的多相模型无膜细胞器的相邻相与RNA的相互作用明显不同。单链和双链RNA优先在同一液滴内的不同阶段积累，并且一个阶段比另一个阶段更不稳定。单相肽滴没有捕捉到这种行为。相共存引入了新的热力学平衡，改变了RNA双链稳定性和杂交状态下的RNA排序。这些效应既不需要生物特异性RNA结合位点，也不需要全长蛋白质。因此，它们更为普遍，指向了现存生物学中运行机制的原始版本，可以帮助理解和设计功能性人工无膜细胞器。
附：英文原文
Title: Phase-specific RNA accumulation and duplex thermodynamics in multiphase coacervate models for membraneless organelles
Author: Choi, Saehyun, Meyer, McCauley O., Bevilacqua, Philip C., Keating, Christine D.
Issue&Volume: 2022-06-30
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.
DOI: 10.1038/s41557-022-00980-7
