Reactome | Formation of the Spliceosomal B complex

Formation of the Spliceosomal B complex

Stable Identifier

R-HSA-9770142

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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The DDX23 RNA helicase (homolog of yeast Prp28) binds ATP to dissociate the 5' splice site of the pre-mRNA from the U1 snRNA, causing displacement of the U1 snRNP from the spliceosome and allowing the 5' splice site to anneal with the U6 snRNA and the 5' exon with the U5 snRNA (Ismaili et al. 2001, Mohlmann et al. 2014, Boesler et al. 2016, Charenton et al. 2019). As annealing between the U6 snRNA and the 5' splice site proceeds, the U4 snRNA previously base-paired with the U6 snRNA becomes available to accommodate SNRNP200 (homolog of yeast Brr2) at the position where it will later dissociate the U4-U6 RNA duplex during subsequent activation. The B complex assembly is further stabilized by the recruitment of several B-specific proteins such as MFAP1, PRP38A, ZMAT2, and WBP4 (FBP21) whose roles have still to be precisely defined. The components of the Spliceosomal B complex have been ascertained using proteomic and structural methods (Rappsilber et al. 2002, Deckert et al. 2006, Bessonov et al. 2008, Wolf et al. 2009, Bessonov et al. 2010, Schmidt et al. 2014, Boesler et al. 2015, Zhang et al. 2018, Charenton et al. 2019, Kastner et al. 2019).

Literature References

PubMed ID	Title	Journal	Year
19536130	Exon, intron and splice site locations in the spliceosomal B complex Lührmann, R, Deckert, J, Stark, H, Merz, C, Kastner, B, Wolf, E	EMBO J	2009
28781166	Cryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for Activation Bertram, K, Will, CL, Lührmann, R, Leelaram, MN, Dybkov, O, Haselbach, D, Agafonov, DE, Stark, H, Urlaub, H, Kastner, B	Cell	2017
26385511	Stable tri-snRNP integration is accompanied by a major structural rearrangement of the spliceosome that is dependent on Prp8 interaction with the 5' splice site Will, CL, Lührmann, R, Rigo, N, Agafonov, DE, Urlaub, H, Boesler, C, Kastner, B	RNA	2015
30975767	Mechanism of 5' splice site transfer for human spliceosome activation Charenton, C, Wilkinson, ME, Nagai, K	Science	2019
16809785	Protein composition and electron microscopy structure of affinity-purified human spliceosomal B complexes isolated under physiological conditions Will, CL, Lührmann, R, Deckert, J, Boehringer, D, Urlaub, H, Stark, H, Behzadnia, N, Kastner, B, Hartmuth, K	Mol. Cell. Biol.	2006
11233976	The 100-kda U5 snRNP protein (hPrp28p) contacts the 5' splice site through its ATPase site Sha, M, Konarska, MM, Gustafson, EH, Ismaïli, N	RNA	2001
12176931	Large-scale proteomic analysis of the human spliceosome. Lamond, AI, Mann, M, Rappsilber, J, Ryder, U	Genome Res	2002
27377154	A spliceosome intermediate with loosely associated tri-snRNP accumulates in the absence of Prp28 ATPase activity Tauchert, MJ, Will, CL, Rigo, N, Anokhina, MM, Agafonov, DE, Luhrmann, R, Urlaub, H, Boesler, C, Ficner, R, Kastner, B	Nat Commun	2016
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
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
18322460	Isolation of an active step I spliceosome and composition of its RNP core Will, CL, Lührmann, R, Anokhina, M, Bessonov, S, Urlaub, H	Nature	2008
24914973	Structural and functional analysis of the human spliceosomal DEAD-box helicase Prp28 Neumann, P, Möhlmann, S, Lührmann, R, Schmitt, A, Ficner, R, Mathew, R	Acta Crystallogr D Biol Crystallogr	2014
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