Abstract

The alternative splicing (AS) of pre-mRNA is an important process in controlling the expression of human genes, which can enrich the diversity of the proteome and regulate gene function. On the contrary, aberrant splicing contributes significantly to numerous human diseases progression, including tumors, neurological diseases, metabolic diseases, infections, and immune diseases. The PUF60, a protein related to RNA splicing, plays critical functions in RNA splicing and gene transcription regulation. In addition, it can achieve synergistic binding with U2AF65 on RNA through interactions in the pyrimidine region, promoting the splicing of introns with weak 3'- splice sites and pyrimidine bundles. Nevertheless, an increasing amount of evidence supports that it shows a significant overexpression pattern in the vast majority of cancer cells and is crucial for embryonic development, indicating that PUF60 may hold the post of a potential therapeutic target for such diseases. These studies have significantly increased our interest in PUF60. Thus, we briefly reviewed the structural domain characteristics of the PUF60, splicing mutants of PUF60, and the roles and functions in human diseases, including various cancers, infections of bacterium and viruses, myositis, and Verheij syndrome. Furthermore, the targeted PUF60 inhibitors and boundedness of the current research were elaborated on in the article. The article effectively communicates critical perception and insight, making it a precious resource for those interested in PUF60 research and treatment.

Keywords: PUF60, FIR, FIRΔexon2, alternative splicing of pre-mRNA, cancer, verheij syndrome.