Meta-Biol

• Pathways

Activation of the Spliceosomal B complex to form the Spliceosomal Bact complex is believed to occur in several complex steps. SNRNP200 (homolog of yeast Brr2) of the U5 snRNP uses ATP to dissociate the U4 snRNP from the spliceosome. This renders U6 snRNA free to form additional interactions with U2 snRNA and fold its internal stem loop to create the active site (Laggerbauer et al. 1998, Lamond et al. 1988, Bessonov et al. 2010, Agafonov et al. 2011, Fica et al. 2013, Galej et al. 2016, Haselbach et al. 2018, Zhang et al. 2018, Kastner et al. 2019). In this active site four phosphate groups of the U6 snRNA cooridinate the two magnesium ions that catalyze both transesterification reactions of pre-mRNA splicing..The PRP19-CDC5L complex (Ajuh et al. 2000, also called the NTC complex) and the PRP19-CDC5L related complex (also called the NTR complex) are recruited during this transition and stabilize the active site (Bessonov et al. 2010, Agafonov et al. 2011, Haselbach et al. 2018, Zhang et al. 2018, Kastner et al. 2019). Splicing does not yet occur because the SF3B1 subunit of the U2 snRNP blocks the branch point and SF3A2 and RNF113A protect the 5' splice site, preventing the intron branch point from reacting with the 5' splice site (Gozani et al. 1996, Gozani et al. 1998, Haselbach et al. 2018, Zhang et al. 2018, Tholen et al. 2022). SNRNP200 and the RES complex retain the SF3B subcomplex in the spliceosome (Haselbach et al. 2018, Zhang et al. 2018). CWC22 recruits EIF4A3, which will form the exon junction complex (EJC) (Busetto et al. 2020) . The components of the Spliceosomal Bact complex have been ascertained using proteomic and structural methods (Bessonov et al. 2010, Agafonov et al. 2011, Haselbach et al. 2018, Zhang et al. 2018, Kastner et al. 2019, Townsend et al. 2020).