A tight couple makes messenger RNAs Gene expression in eukaryotes first requires transcription of DNA to an RNA copy and then splicing to form the final, processed messenger RNA (mRNA). Zhang et al. investigated how gene transcription and RNA splicing are physically coupled. Using cryo–electron microscopy, they resolved the molecular structure of a complex of the transcription enzyme RNA polymerase II with part of the splicing machinery, the U1 small nuclear ribonucleoprotein particle. The results provide important details for our understanding of coupled mRNA production. Science, this issue p. 305 A structure of RNA polymerase II in complex with spliceosomal particle U1 snRNP reveals how transcription and RNA splicing are coupled. To initiate cotranscriptional splicing, RNA polymerase II (Pol II) recruits the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent precursor messenger RNA (pre-mRNA). Here, we report the cryo–electron microscopy structure of a mammalian transcribing Pol II–U1 snRNP complex. The structure reveals that Pol II and U1 snRNP interact directly. This interaction positions the pre-mRNA 5′ splice site near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5′ splice site, leading to the formation of a “growing intron loop.” Loop formation may facilitate scanning of nascent pre-mRNA for the 3′ splice site, functional pairing of distant intron ends, and prespliceosome assembly. Our results provide a starting point for a mechanistic analysis of cotranscriptional spliceosome assembly and the biogenesis of mRNA isoforms by alternative splicing.

中文翻译：

---

转录 RNA 聚合酶 II-U1 snRNP 复合物的结构

一对紧密结合使信使 RNA 真核生物中的基因表达首先需要将 DNA 转录为 RNA 拷贝，然后剪接形成最终的、加工过的信使 RNA (mRNA)。张等人。研究了基因转录和 RNA 剪接是如何物理耦合的。使用低温电子显微镜，他们解析了转录酶 RNA 聚合酶 II 与部分剪接机制（U1 小核核糖核蛋白颗粒）复合物的分子结构。这些结果为我们理解偶联 mRNA 的产生提供了重要的细节。科学，这个问题 p。305 与剪接体颗粒 U1 snRNP 复合的 RNA 聚合酶 II 的结构揭示了转录和 RNA 剪接是如何耦合的。为了启动共转录剪接，RNA 聚合酶 II (Pol II) 将 U1 小核核糖核蛋白颗粒 (U1 snRNP) 募集到新生的前体信使 RNA (pre-mRNA)。在这里，我们报告了哺乳动物转录 Pol II-U1 snRNP 复合物的冷冻电子显微镜结构。该结构表明 Pol II 和 U1 snRNP 直接相互作用。这种相互作用将前 mRNA 5' 剪接位点定位在 Pol II 的 RNA 出口位点附近。pre-mRNA 的延伸保留了 5' 剪接位点，导致形成“不断增长的内含子环”。环的形成可能有助于扫描 3' 剪接位点的新生前 mRNA、远处内含子末端的功能配对和剪接前体组装。我们的结果为共转录剪接体组装和通过选择性剪接的 mRNA 同种型的生物发生的机制分析提供了一个起点。