Laboratory for Transcription Structural Biology, RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
Nat Commun. 2024 Sep 8;15(1):7854. doi: 10.1038/s41467-024-52157-0.
The 5´-3´ exoribonuclease Rat1/Xrn2 is responsible for the termination of eukaryotic mRNA transcription by RNAPII. Rat1 forms a complex with its partner proteins, Rai1 and Rtt103, and acts as a "torpedo" to bind transcribing RNAPII and dissociate DNA/RNA from it. Here we report the cryo-electron microscopy structures of the Rat1-Rai1-Rtt103 complex and three Rat1-Rai1-associated RNAPII complexes (type-1, type-1b, and type-2) from the yeast, Komagataella phaffii. The Rat1-Rai1-Rtt103 structure revealed that Rat1 and Rai1 form a heterotetramer with a single Rtt103 bound between two Rai1 molecules. In the type-1 complex, Rat1-Rai1 forms a heterodimer and binds to the RNA exit site of RNAPII to extract RNA into the Rat1 exonuclease active site. This interaction changes the RNA path in favor of termination (the "pre-termination" state). The type-1b and type-2 complexes have no bound DNA/RNA, likely representing the "post-termination" states. These structures illustrate the termination mechanism of eukaryotic mRNA transcription.
5´-3´外切核糖核酸酶 Rat1/Xrn2 负责终止真核生物 RNA 聚合酶 II 转录。Rat1 与其伴侣蛋白 Rai1 和 Rtt103 形成复合物，并作为“鱼雷”与正在转录的 RNA 聚合酶 II 结合，并将 DNA/RNA 从其解离。在这里，我们报道了来自毕赤酵母的 Rat1-Rai1-Rtt103 复合物和三种 Rat1-Rai1 相关的 RNA 聚合酶 II 复合物（type-1、type-1b 和 type-2）的冷冻电子显微镜结构。Rat1-Rai1-Rtt103 结构表明，Rat1 和 Rai1 形成具有单个 Rtt103 结合在两个 Rai1 分子之间的异四聚体。在 type-1 复合物中，Rat1-Rai1 形成异二聚体并结合到 RNA 聚合酶 II 的 RNA 出口，将 RNA 提取到 Rat1 外切核酸酶活性位点。这种相互作用改变了 RNA 路径，有利于终止（“预终止”状态）。type-1b 和 type-2 复合物没有结合的 DNA/RNA，可能代表“终止后”状态。这些结构说明了真核生物 mRNA 转录的终止机制。
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