Meta-Biol

• Pathways

SF1 bound to the branch point sequence and U2AF bound to the intron polypyrimidine tract and the 3' splice site are present in Spliceosomal E complexes. DDX46 (homolog of yeast Prp5) and UAP56 (homolog of yeast Sub2) displace SF1 and U2AF from the pre-mRNA (Fleckner et al. 1997, Shen et al. 2008)) and recruit the U2 snRNP complex to the branch point of the intron to form the Spliceosomal A complex (Chen et al. 2017). DDX46 bridges the U1 snRNP and U2 snRNP (Xu et al. 2004). The U2 snRNA base pairs with the branch point sequence (Wu and Manley 1989, Tholen et al. 2022) and the branch point adenosine residue is flipped out of the RNA helix and associates with the SF3B1 subunit of the U2 snRNP. The 2' hydroxyl group of the branch point adenosine will act as a nucleophile for the first reaction of splicing but it is shielded at this point by the SF3B subcomplex of the U2 snRNP (Zhang et al. 2020). The components of the Spliceosomal A complex have been ascertained using proteomic and structural methods (Neubauer et al. 1998, Hartmuth et al. 2002, Rappsilber et al. 2002, Behzadnia et al. 2007, Cretu et al. 2021).