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Protein BUD31 homolog (BUD31) is a highly conserved core component of the spliceosome, the molecular complex responsible for the excision of introns from pre-messenger RNA (pre-mRNA) in eukaryotic cells[1][3][6]. BUD31 is essential for proper spliceosome assembly and catalytic activity and interacts with multiple major spliceosomal subcomplexes, including U2 snRNP, U5 snRNP, and associated factors[1][2]. It plays a critical regulatory role in alternative splicing, gene expression, and nuclear receptor coactivation, and binds to exon-intron regions near splicing sites to control exon inclusion[2][4][5][6]. Elevated BUD31 expression is associated with a poor prognosis in several cancers, including ovarian and breast cancer. BUD31 has been identified as a synthetic lethal gene in MYC-driven cancers, and its inhibition can induce apoptosis by disrupting spliceosome function, especially in cancer cells with high MYC activity or spliceosome dependency[1][2]. Pharmacological inhibition of spliceosome activity (such as with SD6) impairs tumorigenicity and metastasis in MYC-driven cancer models and may represent a therapeutic strategy, though the essential nature of splicing in normal cells raises safety concerns for systemic therapy[1].
Inhibition of spliceosome function (for SD6 and spliceosome-targeting therapies)[1] Induction of intron retention and alternative splicing defects leading to cell death in cancer cells[1][2]
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