Zhang Luojia, Batters Christopher, Aibara Shintaro, Gordiyenko Yuliya, Žumer Kristina, Schmitzová Jana, Maier Kerstin, Cramer Patrick, Zhang Suyang
MRC Laboratory of Molecular Biology, Cambridge, UK.
Max Planck Institute for Multidisciplinary Sciences, Department of Molecular Biology, Göttingen, Germany.
Nat Commun. 2025 Jul 1;16(1):5823. doi: 10.1038/s41467-025-60979-9.
In eukaryotic cells, splicing occurs predominantly co-transcriptionally, enhancing splicing efficiency and fidelity while introducing an additional layer of regulation over gene expression. RNA polymerase II (Pol II) facilitates co-transcriptional splicing by recruiting the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to the nascent transcripts. Here, we report the cryo-electron microscopy structure of a transcribing Pol II-U1 snRNP complex with elongation factors DSIF and SPT6. In addition, our biochemical analysis reveals that the phosphorylated Pol II carboxyl-terminal domain and SPT6 interact directly with U1 snRNP proteins, facilitating its recruitment to the elongation complex. This multivalent interaction between U1 snRNP and the transcription elongation complex may both allow efficient spliceosome assembly and ensure transcription processivity.
在真核细胞中，剪接主要在转录同时发生，提高剪接效率和保真度，同时在基因表达上引入额外的调控层次。RNA聚合酶II（Pol II）通过将U1小核核糖核蛋白颗粒（U1 snRNP）招募到新生转录本上促进转录同时剪接。在此，我们报道了带有延伸因子DSIF和SPT6的转录Pol II-U1 snRNP复合物的冷冻电镜结构。此外，我们的生化分析表明，磷酸化的Pol II羧基末端结构域和SPT6直接与U1 snRNP蛋白相互作用，促进其招募到延伸复合物上。U1 snRNP与转录延伸复合物之间的这种多价相互作用可能既允许高效剪接体组装，又确保转录持续性。
