Pre-mRNA-processing-splicing factor 8

Pre-mRNA-processing-splicing factor 8 (PRPF8) is a large scaffolding protein of 2,335 amino acids that plays a central role in pre-mRNA splicing (UniProt: Q6P2Q9). It functions as a core component of both the major U2-type and minor U12-type spliceosomes, mediating the ordered assembly of spliceosomal proteins and snRNAs. PRPF8 positions U2, U5, and U6 snRNAs at splice sites on pre-mRNA substrates, enabling the catalytic splicing reaction.

While UniProt records PRPF8 primarily in association with retinitis pigmentosa 13, a retinal dystrophy caused by PRPF8 mutations, the protein is broadly expressed and essential for splicing across tissues.

In Alzheimer's disease, PRPF8 shows decreased abundance in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Across the analyzed subcellular fractions, PRPF8 displayed a mean log2 fold-change of −0.47, indicating modest downregulation in AD brain (mean log2FC: −0.4679). This reduction in spliceosomal function may have implications for altered splicing patterns in neurodegeneration.