Splicingfaktorer

Splicingfaktorer are proteins that participate in pre-mRNA splicing, the process that removes introns and joins exons to produce mature messenger RNA. They form part of the spliceosome, a dynamic molecular machine composed of small nuclear ribonucleoproteins (snRNPs) and numerous non-snRNP proteins. The core snRNPs are U1, U2, U4, U5 and U6, which assemble on the pre-mRNA with the help of accessory splicing factors to catalyze the two transesterification reactions.

Splicing factors include serine/arginine-rich (SR) proteins, which promote splice site recognition and exon inclusion, and heterogeneous nuclear ribonucleoproteins (hnRNPs), which can repress or modulate splice events. Other critical components are U2AF65 and U2AF35, which bind the polypyrimidine tract and 3' splice site, aiding early assembly. Together, these proteins regulate spliceosome assembly and splice site choice.

Mechanistically, recognition of 5' splice sites by U1, recruitment of U2AF to the 3' site and branch point, and sequential assembly form E, A, B complexes, culminating in a catalytic B* and the two transesterification steps that remove introns and fuse exons. Splicing is often co-transcriptional and influenced by chromatin state and transcription elongation.

Regulation of splicing factors drives alternative splicing, generating diverse mRNA and protein isoforms in a tissue- and condition-specific manner. Misregulation or mutations in splicing factors are linked to diseases, notably cancers with SF3B1, U2AF1 mutations, and inherited disorders such as retinitis pigmentosa caused by PRPF genes.