Formation of the Spliceosomal Bact complex

Stable Identifier
Reaction [uncertain]
Homo sapiens
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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).
Literature References
PubMed ID Title Journal Year
20980672 Characterization of purified human Bact spliceosomal complexes reveals compositional and morphological changes during spliceosome activation and first step catalysis

Sander, B, Will, CL, Lührmann, R, Anokhina, M, Golas, MM, Krasauskas, A, Bessonov, S, Stark, H, Urlaub, H

RNA 2010
29361316 Structure and Conformational Dynamics of the Human Spliceosomal Bact Complex

Komarov, I, Lührmann, R, Graf, B, Dybkov, O, Agafonov, DE, Haselbach, D, Stark, H, Urlaub, H, Kastner, B, Hartmuth, K

Cell 2018
33243851 Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation

Bertram, K, Will, CL, Lührmann, R, Leelaram, MN, Dybkov, O, Agafonov, DE, Stark, H, Urlaub, H, Townsend, C, Kastner, B

Science 2020
34822310 Structural basis of branch site recognition by the human spliceosome

Weis, F, Tholen, J, Galej, WP, Razew, M

Science 2022
8566756 Evidence that sequence-independent binding of highly conserved U2 snRNP proteins upstream of the branch site is required for assembly of spliceosomal complex A

Reed, R, Feld, R, Gozani, O

Genes Dev 1996
32329775 Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes

Paternina, JA, Bensaude, O, Hocq, R, Marquenet, E, Hennion, M, Basquin, J, Le Hir, H, Conti, E, Namane, A, Barbosa, I, Busetto, V

Nucleic Acids Res 2020
9671485 A potential role for U2AF-SAP 155 interactions in recruiting U2 snRNP to the branch site

Reed, R, Potashkin, J, Gozani, O

Mol Cell Biol 1998
11101529 Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry

Lamond, AI, Kuster, B, Mann, M, Zomerdijk, JC, Panov, K, Ajuh, P

EMBO J. 2000
21536652 Semiquantitative proteomic analysis of the human spliceosome via a novel two-dimensional gel electrophoresis method

Will, CL, Lührmann, R, Deckert, J, Odenwälder, P, Agafonov, DE, Bessonov, S, Urlaub, H, Wolf, E

Mol Cell Biol 2011
24196718 RNA catalyses nuclear pre-mRNA splicing

Lu, J, Li, NS, Novak, T, Staley, JP, Dai, Q, Koodathingal, P, Fica, SM, Piccirilli, JA, Tuttle, N

Nature 2013
29360106 Structure of the human activated spliceosome in three conformational states

Shi, Y, Li, L, Yan, C, Zhang, X, Lei, J, Zhan, X

Cell Res 2018
2963332 Spliceosome assembly involves the binding and release of U4 small nuclear ribonucleoprotein

Lamond, AI, Grabowski, PJ, Sharp, PA, Konarska, MM

Proc. Natl. Acad. Sci. U.S.A. 1988
27459055 Cryo-EM structure of the spliceosome immediately after branching

Wilkinson, ME, Fica, SM, Nagai, K, Galej, WP, Newman, AJ, Oubridge, C

Nature 2016
30765414 Structural Insights into Nuclear pre-mRNA Splicing in Higher Eukaryotes

Will, CL, Lührmann, R, Stark, H, Kastner, B

Cold Spring Harb Perspect Biol 2019
9539711 The human U5-200kD DEXH-box protein unwinds U4/U6 RNA duplices in vitro

Achsel, T, Lührmann, R, Laggerbauer, B

Proc Natl Acad Sci U S A 1998
Catalyst Activity

RNA helicase activity of Spliceosomal B complex [nucleoplasm]

Orthologous Events
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