pre-mRNA splicing GENE ONTOLOGYGO:0000398 Reactome Database ID Release 4372163 Reactome, http://www.reactome.org ReactomeREACT_467 The splicing of pre-mRNA occurs within a large, very dynamic complex, designated the 'spliceosome'. The 50-60S spliceosomes are estimated to be 40-60 nm in diameter, and have molecular weights in the range of 3-5 million kDa. Small nuclear RNAs (snRNAs) U1, U2, U4, U5, and U6, are some of the best characterized components of spliceosomes, and are known to play key roles not only in spliceosomal assembly, but also in the two catalytic steps of the splicing reaction. Over 150 proteins have been detected in spliceosomes, and only a subset of these has been characterized. The characterization, and the determination of the functions of the protein components of the spliceosome, is still work in progress.<p>During spliceosome assembly, the snRNAs and the spliceosomal proteins assemble on the pre-mRNA in a stepwise pathway. First the E complex forms, followed by complexes A and B; the C complex forms next and contains the products of the first step of the splicing reaction. Complexes called i and D form as a consequence of the second step of the splicing reaction, which contain the excised intron and the spliced exons, respectively. U2 Dependent Splicing mRNA Splicing - Major Pathway Lariat Formation and 5'-Splice Site Cleavage Formation of the active Spliceosomal C complex Formation of an intermediate Spliceosomal C complex Cleavage at the 3'-Splice Site and Exon Ligation Formation of Exon Junction Complex Formation of the Spliceosomal E complex Formation of the Spliceosomal A Complex Formation of the Spliceosomal B Complex Formation of the Cleavage and Polyadenylation Complex PathwayStep35 PathwayStep34 PathwayStep37 PathwayStep36 PathwayStep39 PathwayStep38 PathwayStep40 PathwayStep32 PathwayStep33