Structural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing
| Autor: | Hua Li, Yunyu Shi, Jerry L. Workman, Ning Zhang, Ying Zhang, Suman Wang, Saikat Bhattacharya, Divya Reddy, Laurence Florens, Michael P. Washburn, Fudong Li, Siyuan Shen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Methyltransferase
RNA Splicing viruses Science genetic processes General Physics and Astronomy Calorimetry Biochemistry environment and public health General Biochemistry Genetics and Molecular Biology Heterogeneous-Nuclear Ribonucleoproteins Mass Spectrometry Article Cell Line SETD2 Humans RNA-Seq Ternary complex Multidisciplinary Crystallography RNA recognition motif Chemistry RNA General Chemistry Histone-Lysine N-Methyltransferase Cell biology RNA splicing Nucleic acid health occupations Leucine Structural biology Protein Binding |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Interaction between SETD2 and hnRNP L has previously been shown to be implicated in coupling gene transcription and mRNA processing. Here the authors elucidate the molecular basis of this functional interaction, showing that the RRM domain of hnRNP L possesses non-overlapping binding interfaces for engaging RNA and SETD2. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink