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.

中文翻译：

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核糖核酸酶 MRP 对前体核糖体 RNA 加工的结构洞察

适应手头的任务 基于 RNA 的催化剂在细胞 RNA 代谢中执行基本任务，尤其是在真核生物中，其中 RNA 被专门的核糖核蛋白 (RNP) 切割，作为核糖体组装或信使 RNA 调节或剪接的一部分。RNA 和蛋白质成分都在塑造这些大型催化复合物如何与其 RNA 底物相互作用方面发挥作用。兰等人。确定了一种称为核糖核酸酶 MRP 的酵母 RNP 的冷冻电子显微镜结构，该结构既可以单独使用，也可以与小 RNA 底物结合。与相关核糖核酸酶 P 的比较揭示了蛋白质和 RNA 成分的差异，这使得核糖核酸酶 MRP 能够识别具有特定序列基序的底物，而不是像核糖核酸酶 P 那样纯粹识别 RNA 结构。这些结构有助于考虑 RNP 如何进化以及为什么它们仍然是真核 RNA 加工的核心。科学，这个问题 p。656 RNA 切割核糖核酸酶 MRP 的结构揭示了通过序列识别底物的基础。核糖核酸酶 (RNase) MRP 是一种保守的真核核糖核蛋白复合物，在前体核糖体 RNA (pre-rRNA) 加工和细胞周期调节中起重要作用。与选择性切割转移 RNA 样底物的 RNase P 相比，RNase MRP 如何识别其不同的底物仍然是个谜。为了解决这个问题，我们确定了单独的酿酒酵母 RNase MRP 和与 pre-rRNA 片段复合的低温电子显微镜结构。这些结构和生化研究的结果表明，蛋白质和 RNA 亚基的共同进化已将 RNase MRP 转化为独特的核糖核酸酶，该酶通过识别短的、松散定义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 可能具有无数尚未识别的底物，它们可以在各种细胞环境中发挥重要作用。