PHD Finger Protein 5A (PHF5A) is a highly conserved protein that plays a crucial role in the regulation of gene expression. It is a member of the plant homeodomain (PHD) finger protein family, which is known for its involvement in chromatin remodeling and transcriptional regulation. The PHD finger domain is a specialized zinc finger motif that can bind to specific histone modifications, acting as an “epigenome reader” to mediate the activation or repression of underlying genes .
PHF5A contains a PHD-finger-like domain flanked by highly basic N- and C-termini. This domain is essential for its function as a chromatin-associated protein. PHF5A is a component of the 17S U2 small nuclear ribonucleoprotein (snRNP) complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs . Within this complex, PHF5A is part of the SF3B subcomplex, which is required for the assembly of the ‘A’ complex formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA .
PHF5A is involved in pre-mRNA splicing, a critical process in gene expression. It directly participates in early spliceosome assembly and mediates the recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing . This function is vital for the accurate and efficient removal of introns from pre-mRNA, ensuring the proper expression of genes.
Recent studies have highlighted the role of PHF5A as an oncoprotein in various cancers, including non-small cell lung cancer (NSCLC). PHF5A has been found to be highly upregulated in lung adenocarcinoma (LAC) tissues compared to adjacent non-tumor tissues . Its expression is closely associated with tumor progression and poor patient prognosis . Functional studies have demonstrated that PHF5A knockdown results in reduced cell proliferation, increased cell apoptosis, cell cycle arrest, and suppressed migration and invasion in LAC cells . These findings suggest that PHF5A contributes to LAC progression by regulating multiple signaling pathways and may serve as a potential therapeutic target in NSCLC .