Formation of the Spliceosomal A complex

Stable Identifier
Reaction [uncertain]
Homo sapiens
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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).
Literature References
PubMed ID Title Journal Year
34301950 Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors

Pena, V, Jurica, M, Gee, P, Larsen, NA, Cretu, C, Nguyen, TV, Agrawal, A, Ghosh, AK, Liu, X, Cook, A

Nat Commun 2021
14713954 Prp5 bridges U1 and U2 snRNPs and enables stable U2 snRNP association with intron RNA

Kameoka, S, Xu, YZ, Huang, T, Query, CC, Newnham, CM, Konarska, MM

EMBO J 2004
12477934 Protein composition of human prespliceosomes isolated by a tobramycin affinity-selection method.

Hartmuth, K, Urlaub, H, Lührmann, R, Gentzel, M, Wilm, M, Vornlocher, HP, Will, CL

Proc Natl Acad Sci U S A 2002
32494006 Molecular architecture of the human 17S U2 snRNP

Bertram, K, Will, CL, Lührmann, R, Dybkov, O, Agafonov, DE, Stark, H, Urlaub, H, Kastner, B, Zhang, Z, Hofele, R, Hartmuth, K

Nature 2020
18593880 Distinct activities of the DExD/H-box splicing factor hUAP56 facilitate stepwise assembly of the spliceosome

Zhang, L, Shen, J, Zheng, X, Shen, H, Zhao, R, Green, MR

Genes Dev 2008
2558966 Mammalian pre-mRNA branch site selection by U2 snRNP involves base pairing

Manley, JL, Wu, J

Genes Dev 1989
34822310 Structural basis of branch site recognition by the human spliceosome

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

Science 2022
17332742 Composition and three-dimensional EM structure of double affinity-purified, human prespliceosomal A complexes

Sander, B, Will, CL, Lührmann, R, Deckert, J, Golas, MM, Dube, P, Stark, H, Urlaub, H, Behzadnia, N, Kastner, B, Hartmuth, K

EMBO J. 2007
12176931 Large-scale proteomic analysis of the human spliceosome.

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

Genome Res 2002
9731529 Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex

Neubauer, G, Calvio, C, Rappsilber, J, Sleeman, J, Watson, M, Lamond, A, King, A, Mann, M, Ajuh, P

Nat. Genet. 1998
9242493 U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction

Valcárcel, J, Green, MR, Fleckner, J, Zhang, M

Genes Dev 1997
27683217 Stoichiometries of U2AF35, U2AF65 and U2 snRNP reveal new early spliceosome assembly pathways

Vorechovsky, I, Hudson, AJ, Eperon, IC, Chen, L, Kralovicova, J, Weinmeister, R, Eperon, LP

Nucleic Acids Res 2017
Catalyst Activity

RNA helicase activity of Spliceosomal E complex [nucleoplasm]

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