PRPF8

PRPF8, or pre-mRNA processing factor 8, is a eukaryotic protein that functions as a core component of the U5 small nuclear ribonucleoprotein particle in the spliceosome. It is one of the largest and most conserved splicing factors and is essential for viability in many organisms. In human cells, PRPF8 is predominantly nuclear, where it associates with snRNPs and spliceosomal complexes during pre-mRNA processing.

PRPF8 acts as a central scaffold for the catalytic core of the spliceosome, coordinating the two transesterification steps of intron removal. It interacts with the U5 snRNA and with multiple proteins from the U2/U4/U6 snRNPs, helping to position the 5' splice site, branch point, and 3' splice site for catalysis. The protein participates in spliceosome assembly, activation, and structural rearrangements that accompany splicing.

PRPF8 is a large, multi-domain protein. Its central region contains a protease-like, RNase H–related domain that provides a structural scaffold for the active site, while other regions mediate protein–protein and protein–RNA interactions. The domain organization is highly conserved from yeast to humans, reflecting its essential role in splicing.

PRPF8 is evolutionarily conserved and broadly expressed, consistent with a universal role in mRNA processing. Its function in maintaining accurate and efficient splicing has made it a focus of studies on spliceosome architecture and regulation.