上海交通大学医学院雷鸣、武健等研究人员合作解析出核糖核酸酶MRP加工rRNA前体的机制。该项研究成果发表于2020年6月25日在线发表在《科学》杂志上。

据研究人员介绍，核糖核酸酶（RNase）MRP是一种保守的真核核糖核蛋白复合物，在前核糖体RNA（pre-rRNA）加工和细胞周期调控中起重要作用。与选择性切割tRNA样底物的RNase P相比，RNase MRP如何识别其多种底物仍然是个谜。

为了解决这个问题，研究人员解析了酿酒酵母RNase MRP以及与pre-rRNA片段结合的冷冻电镜结构。这些结构与生化研究相结合，揭示了蛋白质和RNA亚基的共同进化已将RNase MRP转化为一种独特的核糖核酸酶，其通过识别短而非精确的共有序列来处理单链RNA。这种广泛的底物特异性表明RNase MRP可能具有无数但尚未鉴定的底物，这些底物可能在各种细胞环境中发挥重要作用。

附：英文原文

Title: Structural insight into precursor ribosomal RNA processing by ribonuclease MRP

Author: Pengfei Lan, Bin Zhou, Ming Tan, Shaobai Li, Mi Cao, Jian Wu, Ming Lei

Issue&Volume: 2020/06/25

Abstract: Abstract Ribonuclease (RNase) MRP is a conserved eukaryotic ribonucleoprotein complex that plays essential roles in pre-ribosomal RNA (pre-rRNA) processing and cell cycle regulation. In contrast to RNase P, which selectively cleaves tRNA-like substrates, it has remained a mystery how RNase MRP recognizes its diverse substrates. To address this question, we determined cryo-EM structures of Saccharomyces cerevisiae RNase MRP alone and in complex with a fragment of pre-rRNA. These structures combined with biochemical studies reveal that co-evolution of both protein and RNA subunits has transformed RNase MRP into a distinct ribonuclease that processes single-stranded RNAs by recognizing a short, loosely-defined consensus sequence. This broad substrate specificity suggests that RNase MRP may have myriad yet unrecognized substrates that could play important roles in various cellular contexts.

DOI: 10.1126/science.abc0149

Source: https://science.sciencemag.org/content/early/2020/06/24/science.abc0149