Structural insight into precursor ribosomal RNA processing by ribonuclease MRP

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 Saccharomyces cerevisiae 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是一种保守的真核生物核糖核蛋白复合物，在前体核糖体RNA（pre - rRNA）加工和细胞周期调控中发挥关键作用。与选择性切割类转运RNA底物的RNase P不同，RNase MRP如何识别其多样的底物一直是个谜。为了解决这个问题，我们测定了酿酒酵母（Saccharomyces cerevisiae）RNase MRP单独以及与pre - rRNA片段复合时的冷冻电镜结构。这些结构以及生化研究结果表明，蛋白质和RNA亚基的共同进化已使RNase MRP转变为一种独特的核糖核酸酶，它通过识别一个短的、定义宽松的共有序列来加工单链RNAs。这种广泛的底物特异性表明，RNase MRP可能有无数尚未被识别的底物，这些底物可能在各种细胞环境中发挥重要作用。