Spliceosomes

Spliceosomes are large ribonucleoprotein complexes that catalyze pre-mRNA splicing in eukaryotic nuclei. They remove introns and join exons to produce mature mRNA. Most introns are removed by the major (U2-type) spliceosome, while a minority are processed by the minor (U12-type) spliceosome. Core components include five small nuclear RNAs (snRNAs) – U1, U2, U4, U5, and U6 – each assembled with proteins as snRNPs. The minor spliceosome uses U11, U12, U4atac, U6atac, and U5 in place of several of the major snRNAs.

Spliceosome assembly proceeds through ordered steps: recognition of the 5' splice site by U1 and the branch point by U2 forms the A complex; recruitment of the U4/U6.U5 tri-snRNP forms the B complex; ATP-dependent rearrangements generate the catalytically active C complex. The reaction occurs via two transesterifications. First, the branch point A attacks the 5' splice site, creating a lariat and a split exon; second, the 3' OH of the upstream exon attacks the 3' splice site, joining exons and releasing the intron as a lariat. The snRNPs dissociate and recycle.

Splicing is regulated by cis-acting RNA elements and trans-acting proteins that influence splice-site choice, including alternative splicing. Spliceosome activity is coupled to transcription and occurs in the nucleus. Mutations in splicing factors or snRNP components are linked to diseases such as retinitis pigmentosa and various cancers. The spliceosome is evolutionarily conserved and thought to originate from group II introns.