Figure 2.

The spliceosome assembly cycle. Through interactions with various proteins that recognise specific splice site features, the spliceosome components, that is, small nuclear ribonucleoproteins (snRNPs) designated with U1, U2, U4, U5 and U6 are sequentially recruited to the splice site and assembled into the spliceosome. Once completed, splicing is catalysed in two consecutive transesterification reactions. In the initial step, the 2′ OH group of the branch point adenosine upstream of the 3′ end of the intron reacts with the 5′ splice junction, forming a novel 2′, 5′ phosphodiester bond between the branch point and the 5′ terminal nucleotide of the intron, giving rise to a lariat structure. In the second reaction, the 3′ OH of the 5′ exon attacks the 3′ splice junction producing linked 5′ and 3′ exons and liberating the intron. Subsequently, the snRNPs involved are released and recycled in the splicing process. In the top right-hand corner, a detailed view of U2 snRNP with subcomplexes, SF3a and SF3b, is shown. The spliceosome-associated proteins (SAP) 130 and/or 155 are targeted by pladienolide derivatives (a.o. E-7107) and spliceostatin A.