Duc Ngu / Chemistry & Biochemistry / Faculty Mentor: Byung Ran So
In eukaryotes, precursor messenger RNA (pre-mRNA) undergoes multiple post-transcriptional processes to produce mature mRNA, a crucial intermediate in the flow of genetic information from DNA to protein expression. Small nuclear ribonucleoproteins (snRNPs) play a key role in spliceosome-mediated pre-mRNA splicing, facilitating the joining of coding exons and the removal of non-coding introns. U1 snRNP is one of the most abundant in human (HeLa) cells and is essential for both splicing and preventing premature transcription termination, a process known as telescripting. To investigate the functional role of U1 snRNP-specific proteins in U1 snRNP assembly, we established an in vitro U1 snRNP reconstitution system and found that U1C, a U1 snRNP-specific protein that stabilizes U1 snRNP binding to pre-mRNAs, is essential for U1 snRNP assembly. Additionally, we developed a dual-luciferase reporter system to monitor splicing and telescripting using engineered U1 snRNPs with alternative pre-mRNA bindings. Furthermore, we initiated in vitro system to detect liquid-liquid phase separation, utilizing the disordered and low complexity domains of U1 snRNP-specific proteins in their interaction with SMN complex during snRNP biogenesis. Our ongoing studies aim to elucidate that the role of U1 snRNP-specific proteins in U1 snRNP assembly and their broader interactions in splicing and telescripting regulation.
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