Structural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing
Structural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing
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SETD2甲基转移酶和hnRNP L旁系同源物之间相互作用控制共转录剪接的结构基础
DOI：
10.1101/2021.05.22.445248
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Jerry L. Workman
中科院分区：
文献类型：
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作者：
Saikat Bhattacharya;Suman Wang;Divya Reddy;Siyuan Shen;Ying Zhang;Ning Zhang;Hua Li;Michael P. Washburn;Laurence Florens;Yunyu Shi;Fudong Li;Jerry L. Workman
RNA识别基序（RRM）与核酸以及蛋白质结合。在前mRNA加工hnRNP蛋白中发现了不止一个这样的结构域。虽然RRM识别RNA的模式是已知的，但它们与蛋白质相互作用的分子基础仍然不清楚。在这里，我们描述了hnRNP L和LL与甲基转移酶SETD 2之间的相互作用模式。我们证明，对于发生的相互作用，亮氨酸对内的一个高度保守的延伸的SETD 2插入其侧链在疏水口袋中形成的hnRNP L RRM 2。值得注意的是，该结构还强调RRM 2可以与SETD 2和RNA形成三元复合物。值得注意的是，突变SETD 2中的亮氨酸对也会导致其与其他hnRNP的相互作用减少。重要的是，SETD 2-hnRNP L相互作用模式与其他相关蛋白质-蛋白质相互作用的相似性揭示了剪接调节子相互作用的保守设计。
The RNA recognition motif (RRM) binds to nucleic acids as well as proteins. More than one such domain is found in the pre-mRNA processing hnRNP proteins. While the mode of RNA recognition by RRMs is known, the molecular basis of their protein interaction remains obscure. Here we describe the mode of interaction between hnRNP L and LL with the methyltransferase SETD2. We demonstrate that for the interaction to occur, a leucine pair within a highly conserved stretch of SETD2 insert their side chains in hydrophobic pockets formed by hnRNP L RRM2. Notably, the structure also highlights that RRM2 can form a ternary complex with SETD2 and RNA. Remarkably, mutating the leucine pair in SETD2 also results in its reduced interaction with other hnRNPs. Importantly, the similarity that the mode of SETD2-hnRNP L interaction shares with other related protein-protein interactions reveals a conserved design by which splicing regulators interact with one another.