The production of messenger RNA in eukaryotic cells involves precursor mRNA (pre-mRNA) synthesis and processing. During splicing, the spliceosome removes introns from the pre-mRNA in a co-transcriptional manner on the surface of RNA polymerase II (Pol II). Co-transcriptional splicing enhances the efficiency and accuracy of splicing. Conversely, splicing factors have been suggested to regulate transcription elongation speed and to prevent premature transcription termination. The tightly coordinated crosstalk between the transcription and splicing machineries enhances the fidelity of gene expression and is thus important for cell survival and functionality. Dysregulation of co-transcriptional splicing is involved in cancer pathogenesis and is being investigated as a potential biomarker for disease diagnosis and prognosis
Our lab’s research focuses on how the transcription and splicing machineries crosstalk to regulate gene expression in human. We previously determined the cryo-EM structure of a transcribing Pol II-U1 snRNP complex, where U1 snRNP is the first spliceosomal building block to engage the pre-mRNA. The structure reveals a direct physical interaction between Pol II and U1 snRNP, positioning the 5’ splice site at the RNA exit site of Pol II, and providing mechanistic insights into the first step of co-transcriptional splicing. Recently, our work demonstrates that U1 snRNP is recruited to elongating Pol II through additional interactions with transcription elongation factors. Furthermore, we identified a regulatory mechanism that modulates Pol II elongation rate, potentially facilitating the coordination of co-transcriptional processes.
This PhD project aims to understand the molecular interactions between the transcription and splicing machineries and how these interactions facilitate efficient and accurate splicing. Successful candidate will gain experiences and knowledge in in vitro reconstitution of large protein-nucleic acid complexes, working with mammalian cells, biochemical assays and the cutting-edge structural biology with a focus on cryo-electron microscopy. Please feel free to contact me for more detailed discussion of the project.
References
Structure of a transcribing RNA polymerase II–U1 snRNP complex
Science 371(6526): 305-309 (2021)
Structural basis of RECQL5-induced RNA polymerase II transcription braking and subsequent reactivation.
Nat Struct Mol Biol: (2025)
Structure of a transcribing Pol II-DSIF-SPT6-U1 snRNP complex.
Nat Commun 16(1): 5823 (2025) Epub
RNA Polymerase II Phosphorylated on CTD Serine 5 Interacts with the Spliceosome during Co-transcriptional Splicing
Molecular Cell 72(2): 369-379.e4 (2018)
Transcription and splicing: A two‐way street
WIREs RNA 11(5): (2020)