State Key Laboratory of Oncogenes and Related Genes, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Shanghai Institute of Precision Medicine, Shanghai 200125, China.
Science. 2020 Aug 7;369(6504):656-663. doi: 10.1126/science.abc0149. Epub 2020 Jun 25.
Ribonuclease (RNase) MRP is a conserved eukaryotic ribonucleoprotein complex that plays essential roles in precursor ribosomal RNA (pre-rRNA) processing and cell cycle regulation. In contrast to RNase P, which selectively cleaves transfer RNA-like substrates, it has remained a mystery how RNase MRP recognizes its diverse substrates. To address this question, we determined cryo-electron microscopy structures of RNase MRP alone and in complex with a fragment of pre-rRNA. These structures and the results of biochemical studies reveal that coevolution 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.
核糖核酸酶（RNase）MRP 是一种保守的真核核糖核蛋白复合物，在核糖体 RNA（pre-rRNA）前体加工和细胞周期调控中发挥着重要作用。与选择性切割 tRNA 样底物的 RNase P 不同，RNase MRP 如何识别其多样化的底物一直是个谜。为了解决这个问题，我们测定了 RNase MRP 单独存在和与 pre-rRNA 片段形成复合物的冷冻电子显微镜结构。这些结构和生化研究的结果表明，蛋白质和 RNA 亚基的共同进化将 RNase MRP 转变成一种独特的核糖核酸酶，通过识别短的、定义不严格的共识序列来加工单链 RNA。这种广泛的底物特异性表明，RNase MRP 可能有许多尚未被识别的底物，这些底物可能在各种细胞环境中发挥着重要作用。
