FIGURE 1: Major versus minor intron splicing. (A) Major (U2-type) and minor (U12-type) introns differ in their cis-acting 5’ss and BPS elements. The (nearly) invariant nucleotides are highlighted in red letters. Non-coloured letters indicate a clear preference for a nucleotide at a given position and potential base parings with the respective snRNAs are depicted. Base modifications of snRNAs are omitted. Minor introns are subdivided into AT-AC or GT-AG minor introns based on their termi-nal dinucleotides. (B) Major and minor introns are recognized differently by their respective spliceosomes, which assemble on their substrates in a stepwise manner. Major introns are initially recognized by the U1 snRNP binding to the 5’ splice site, SF1 binding to the branch point sequence (BPS) and U2AF2/1 heterodimer recognizing the polypyrimidine tract (PPT) and the 3’ terminal AG dinucleotide, respectively. Recognition of the BPS by the U2 snRNA displaces the SF1 and converts the E complex to complex A. In contrast to the major introns, 5’ss and BPS of minor introns are recognized cooperatively by U11 and U12 of the di-snRNP, respectively, thereby forming the minor intron A complex. The subsequent steps in the splicing process are very similar between the two systems and intron recognition is followed by the association of major and minor tri-snRNPs, respectively, giving rise to (presumably) similar catalytic structures and catalytic steps of splicing.