Bud31, also known as Functional Spliceosome-Associated Protein 17, is a spliceosome component. It is involved in pre-mRNA splicing and processing, and acts as a transcriptional regulator of androgen receptor (AR) target genes. Its functions are crucial in various biological processes related to cell cycle regulation and development [3,5,6,7].

In mice, germ-cell-specific knockout of Bud31 led to loss of spermatogonia and male infertility, indicating its essential role in spermatogonial stem cell pool maintenance and the initiation of spermatogenesis. Deletion of Bud31 in germ cells caused widespread exon-skipping and intron retention, with Cdk2 identified as one of its direct splicing targets. Knockout of Bud31 resulted in retention of the first intron of Cdk2 and a decrease in Cdk2 expression [1].

In ovarian cancer, BUD31 is increased, and its higher expression predicts worse prognosis. Inhibition of BUD31 led to extensive exon skipping, and it was found to sustain the expression of anti-apoptotic BCL2L12 by stimulating the inclusion of exon 3. Knockdown of BUD31 promoted exon 3 skipping of BCL2L12, leading to apoptosis of ovarian cancer cells [2].

In clear cell renal cell carcinoma (ccRCC), BUD31 is upregulated, and high expression correlates with worse survival outcomes, increased genomic instability, and a less active immune microenvironment. BUD31 knockdown inhibited cell proliferation, migration, and invasion in vitro and reduced tumor growth in vivo. RNA sequencing identified 390 alternative splicing events regulated by BUD31, including 17 cell cycle-related genes [4].

In conclusion, Bud31 is vital for processes such as spermatogenesis, and its dysregulation is associated with cancers like ovarian cancer and ccRCC. Gene-knockout mouse models have been instrumental in revealing its role in these biological processes and disease conditions, providing insights into potential therapeutic targets for related diseases.