Structural insight into precursor ribosomal RNA processing by ribonuclease MRP
Structural insight into precursor ribosomal RNA processing by ribonuclease MRP
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核糖核酸酶 MRP 对前体核糖体 RNA 加工的结构洞察
DOI：
10.1126/science.abc0149
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发表时间：
2020-08-07
期刊：
影响因子：
56.9
通讯作者：
Lei, Ming
中科院分区：
文献类型：
--
作者：
Lan, Pengfei;Zhou, Bin;Lei, Ming
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。
Adapted to the task at hand RNA-based catalysts perform fundamental tasks in cellular RNA metabolism, especially in eukaryotes, where RNAs are cut by specialized ribonucleoproteins (RNPs) as part of ribosome assembly or messenger RNA regulation or splicing. Both RNA and protein components play a role in shaping how these large catalytic complexes interact with their RNA substrates. Lan et al. determined the cryo–electron microscopy structures of a yeast RNP called ribonuclease MRP both alone and bound to a small RNA substrate. Comparison with the related ribonuclease P revealed differences in both protein and RNA components that enable ribonuclease MRP to recognize substrates with a specific sequence motif, rather than purely recognizing RNA structure as ribonuclease P does. These structures aid in considering how RNPs evolved and why they remain central to eukaryotic RNA processing. Science, this issue p. 656 Structures of the RNA-cleaving ribonuclease MRP reveal the basis for substrate recognition by sequence. 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.