Ayesha Ali Khan / Chemistry & Biochemistry / Faculty Mentor: Byung Ran So
MYC, a proto-oncogene, regulates cellular growth and proliferation by controlling the transcription and translation of core spliceosome components. 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. Under normal conditions, MYC ensures a sufficient supply of small nuclear ribonucleoproteins (snRNPs), major components of the spliceosome. However, MYC hyperactivation increases pre-mRNA levels beyond the spliceosome’s processing capacity, leading to pre-mRNA accumulation and deregulation of essential genes. This may create a bottleneck at the snRNP biogenesis step, where the production of mature snRNPs cannot keep pace. This imbalance could result in defective spliceosome assembly and aberrant mRNA splicing.
To investigate this vulnerability, we used mammary epithelial cell lines engineered with an estrogen receptor to induce MYC hyperactivation. We assessed the abundance of the SMN complex, a multi-component chaperone that assembles Sm rings on snRNAs, a critical step in snRNP stability and function. By evaluating this process, we aim to elucidate how MYC-driven dysregulation of snRNP biogenesis contributes to splicing stress. Our findings will provide insights into how MYC hyperactivation disrupts pre-mRNA processing, highlighting splicing stress as a therapeutic strategy in MYC-driven malignancies.
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