Sanat Myti / Chemistry & Biochemistry / Faculty Mentor: Byung Ran So
The spliceosome is a macromolecular RNA-Protein complex that catalyzes splicing, a two-step reaction that converts precursor
messenger RNA (pre-mRNA) into mature mRNA—an essential intermediate in gene-to-protein expression. Although
spliceosome assembly requires equal stoichiometry of snRNPs, the abundance and repertoire of small nuclear ribonucleoprotein complexes (snRNPs) vary significantly in a tissue- and development-specific manner. Among snRNPs, U4 snRNP is crucial for spliceosome activation and regulation, yet given its critical role in ensuring splicing fidelity, function, and human health, the mechanism governing its biogenesis remain poorly understood. Here, we examined the interaction between U4 snRNP-specific proteins and the SMN complex, a multi-component RNP chaperone responsible for assembling an Sm core on each snRNA and ensuring the stability of snRNP biogenesis. Depletion of U4 snRNP-specific snRNP27 reduced U4 snRNA levels drastically and impaired its interaction with the SMN complex. Moreover, our findings reveal that it not only reduces U4
snRNP assembly but also affects the assembly of other snRNPs. These results suggest that snRNP-specific proteins regulate snRNP abundance by either promoting canonical snRNP assembly or stabilizing snRNPs, a process mediated by the SMN complex. Given the role of U4 snRNPspecific proteins in spliceosome stability, dysregulation might contribute to splicing diseases, and it could be considered a potential target for the further investigation of RNA processing disorders.
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