Formation of the Spliceosomal B* complex

Stable Identifier
Reaction [uncertain]
Homo sapiens
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DHX16 (homolog of yeast Prp2) hydrolyzes ATP in the Spliceosomal Bact complex to form the Spliceosomal B* complex (Gencheva et al. 2010), possibly by pulling the intron to dissociate the RES complex and the SF3A and SF3B subcomplexes of the U2 snRNP from the spliceosome (Bessonov et al. 2010, Agafonov et al. 2011, Schmidt et al. 2014, Kastner et al. 2019). The intron branch point now docks near the 5' splice site (Zhan et al. 2018), displacing RNF113A (homolog of yeast Cwc24) (Schmidt et al. 2014, Zhan et al. 2018). YJU2 and ISY1 bind and distort the helix of the branch point to fit the active site (Zhan et al. 2018). Prior to the transesterification reaction between the adenosine residue of the intron branch point and the 5' splice site, the complex is called the Spliceosomal B* complex.
Components of the core exon junction complex (EJC) comprising EIF4A3, CASC3, MAGOH, and RBM8A are recruited to the spliceosome around this time (Kataoka and Dreyfuss 2004) by an interaction between CWC22 and EIF4A3 (Reichert et al. 2002, Alexandrov et al. 2012, Barbosa et al. 2012, Steckelberg et al. 2012, Busetto et al. 2020), though they may not yet bind RNA. CWC27 must be displaced in order for RBM8A (Y14) to bind (Busetto et al. 2020). Due to the position of CWC22 in the spliceosome, the EJC will be deposited on the 5' exon about 20-24 nucleotides upstream of the 5' splice site. The components and formation of the spliceosomal B* complex are partly inferred from the composition of the spliceosomal C complex (Jurica et al. 2002, Makarov et al. 2002, Rappsilber et al. 2002, Reichert et al. 2002, Bessonov et al. 2010, Agafonov et al. 2011, Schmidt et al. 2014, Zhan et al. 2018, Kastner et al. 2019).

Literature References
PubMed ID Title Journal Year
11991638 Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis.

Grigorieff, N, Moore, MJ, Licklider, LJ, Gygi, SR, Jurica, MS

RNA 2002
12414731 5' exon interactions within the human spliceosome establish a framework for exon junction complex structure and assembly

Moore, MJ, Reichert, VL, Jurica, MS, Le, Hir H

Genes Dev 2002
23236153 Human spliceosomal protein CWC22 plays a role in coupling splicing to exon junction complex deposition and nonsense-mediated decay

Shu, MD, Alexandrov, A, Colognori, D, Steitz, JA

Proc Natl Acad Sci U S A 2012
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
22961380 Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly

Barrandon, C, Haque, N, Le Hir, H, Barbosa, I, Blanchette, M, Fiorini, F, Tomasetto, C

Nat Struct Mol Biol 2012
29301961 Structure of a human catalytic step I spliceosome

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

Science 2018
20423332 Contribution of DEAH-box protein DHX16 in human pre-mRNA splicing

Gencheva, M, Kato, M, Newo, AN, Lin, RJ

Biochem. J. 2010
12176931 Large-scale proteomic analysis of the human spliceosome.

Lamond, AI, Mann, M, Rappsilber, J, Ryder, U

Genome Res 2002
22959432 CWC22 connects pre-mRNA splicing and exon junction complex assembly

Gehring, NH, Steckelberg, AL, Boehm, V, Gromadzka, AM

Cell Rep 2012
14625303 A simple whole cell lysate system for in vitro splicing reveals a stepwise assembly of the exon-exon junction complex

Kataoka, N, Dreyfuss, G

J Biol Chem 2004
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
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
24448447 Mass spectrometry-based relative quantification of proteins in precatalytic and catalytically active spliceosomes by metabolic labeling (SILAC), chemical labeling (iTRAQ), and label-free spectral count

Lührmann, R, Deckert, J, Schmidt, C, Bessonov, S, Urlaub, H, Conrad, T, Grønborg, M

RNA 2014
12411573 Small nuclear ribonucleoprotein remodeling during catalytic activation of the spliceosome

Makarova, OV, Will, CL, Gentzel, M, Lührmann, R, Wilm, M, Makarov, EM, Urlaub, H

Science 2002
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
Catalyst Activity

RNA helicase activity of Spliceosomal Bact complex [nucleoplasm]

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