近日，美国康奈尔大学Lois Pollack团队报道了核苷酸特异性RNA构象和动力学作为核糖核蛋白凝聚体的前体。该研究于2025年9月29日发表在《美国化学会志》上。

核糖核蛋白（RNP）凝聚体具有独特的生理和病理意义，但其内部RNA的结构尚不清楚。使用对比变化溶液x射线散射（仅识别蛋白质-RNA复合物中的RNA结构），以及基于集成的结构建模，poly-U和poly-A RNA与多碱肽相互作用时的构象变化被表征。

研究组使用粗粒度分子动力学模拟阐明RNP凝聚体内的RNA动力学。在高盐条件下，肽-RNA结合较弱，在亚饱和条件下可以观察到RNA结构的变化。在较低的盐浓度下，关联增强，在相分离的RNP混合物中只检测到poly-A RNA的位置顺序。该方法也适用于研究CAG和CUG三核苷酸重复序列，无论是单独的还是与肽的复合物。RNA结合通过多肽的加入而增强，并且在poly-A系统中，这些基序表现出位置排序。

附：英文原文

Title: Nucleotide-Specific RNA Conformations and Dynamics as Precursors to Ribonucleoprotein Condensates

Author: Tong Wang, Qingyue Hu, Scout Fronhofer, Lois Pollack

Issue&Volume: September 29, 2025

Abstract: Ribonucleoprotein (RNP) condensates have distinct physiological and pathological significance, but the structure of RNA within them is not well understood. Using contrast-variation solution X-ray scattering, which discerns only the RNA structures within protein-RNA complexes, alongside ensemble-based structural modeling, conformational changes of poly-U and poly-A RNA are characterized as they interact with polybasic peptides. Coarse-grained molecular dynamics simulations are used to elucidate RNA dynamics within RNP condensates. At high salt, where peptide-RNA association is weak, RNA structural changes are discerned at subsaturated conditions. At lower salt concentrations, where association is enhanced, positional order of only poly-A RNA is detected within phase separated RNP mixtures. This method is also applied to study trinucleotide CAG and CUG repeats, alone and in complex with peptides. RNA association is enhanced by the addition of peptides and, as in the poly-A system, these motifs exhibit positional ordering.

DOI: 10.1021/jacs.5c05892

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c05892