美国俄亥俄州立大学Banerjee, Priya R.团队报道了RNA在较低的临界溶液温度下发生相变。相关研究成果于2023年11月6日发表在《自然—化学》。

RNA和RNA结合蛋白的共相分离驱动核糖核蛋白颗粒的生物发生。RNA也可以在没有蛋白质的情况下发生相变。然而，不含蛋白质、RNA驱动的相变的物理化学驱动力仍不清楚。

该文中，研究人员报道了各种类型的RNA在系统特定的较低临界溶液温度下进行相分离。这种熵驱动的相分离是磷酸根骨架的固有特征，需要Mg²⁺离子，并由RNA碱基调节。仅含RNA的缩合物可以在致密相中另外经历焓有利的渗滤转变。这是通过磷酸基团与RNA特异性碱基堆叠，和碱基配对之间的Mg²⁺依赖性桥接相互作用的组合实现的。相分离结合渗滤可以导致RNA在缩合物中的动态停滞，并抑制RNase P核酶的催化活性。

该工作强调了将RNA驱动的相变纳入核糖核蛋白颗粒生物发生模型的必要性。不含蛋白质、RNA驱动的相变的物理化学驱动力以前尚不清楚，但现在表明，在镁离子存在下加热时，RNA会经历熵驱动的液-液相分离。在凝聚相中，RNA可以经历焓有利的渗滤转变，从而导致滞留冷凝物。

附：英文原文

Title: RNAs undergo phase transitions with lower critical solution temperatures

Author: Wadsworth, Gable M., Zahurancik, Walter J., Zeng, Xiangze, Pullara, Paul, Lai, Lien B., Sidharthan, Vaishnavi, Pappu, Rohit V., Gopalan, Venkat, Banerjee, Priya R.

Issue&Volume: 2023-11-06

Abstract: Co-phase separation of RNAs and RNA-binding proteins drives the biogenesis of ribonucleoprotein granules. RNAs can also undergo phase transitions in the absence of proteins. However, the physicochemical driving forces of protein-free, RNA-driven phase transitions remain unclear. Here we report that various types of RNA undergo phase separation with system-specific lower critical solution temperatures. This entropically driven phase separation is an intrinsic feature of the phosphate backbone that requires Mg2+ ions and is modulated by RNA bases. RNA-only condensates can additionally undergo enthalpically favourable percolation transitions within dense phases. This is enabled by a combination of Mg2+-dependent bridging interactions between phosphate groups and RNA-specific base stacking and base pairing. Phase separation coupled to percolation can cause dynamic arrest of RNAs within condensates and suppress the catalytic activity of an RNase P ribozyme. Our work highlights the need to incorporate RNA-driven phase transitions into models for ribonucleoprotein granule biogenesis. The physicochemical driving forces of protein-free, RNA-driven phase transitions were previously unclear, but it is now shown that RNAs undergo entropically driven liquid–liquid phase separation upon heating in the presence of magnesium ions. In the condensed phase, RNAs can undergo an enthalpically favourable percolation transition that leads to arrested condensates.

DOI: 10.1038/s41557-023-01353-4

Source: https://www.nature.com/articles/s41557-023-01353-4