Reactome | Formation of the Spliceosomal E complex

Formation of the Spliceosomal E complex

Stable Identifier

R-HSA-9770119

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Splicing of pre-mRNAs occurs co-transcriptionally in mammals. The U1 snRNP, comprising the U1 snRNA, Sm ring, SNRNP70, SNRPA, and SNRPC, interacts with RNA polymerase II (Zhang et al. 2021) and binds the 5' splice site of the nascent pre-mRNA to initiate formation of the early spliceosomal complex (Spliceosomal E complex) (Zhuang and Weiner 1986, Kondo et al. 2015, Tan et al. 2016). Binding of the U1 snRNA to the pre-mRNA is mediated by base-pairing between the U1 snRNA and the 5' splice site. The zinc finger of SNRPC also binds the pre-RNA to stabilize the interaction (Kondo et al. 2015). Within the Spliceosomal E complex, SF1 binds the branch point within the intron and pre-bulges the adenosine residue of the branch point (Crisci et al. 2015). The U2AF1:U2AF2 heterodimer (also called the U2AF35:U2AF65 heterodimer or the U2AF complex) binds the polypyrimidine tract of the intron and the 3' splice site (Berglund et al. 1998). The U2 snRNP complex may be loosely associated with the Spliceosomal E complex but does not yet bind the pre-mRNA (Hong et al. 1997, Das et al. 2000). Most alternative splicing factors bind the pre-mRNA prior to formation of the Spliceosomal E complex and influence the selection of the splice sites by interacting with components of the spliceosome. The components of the Spliceosomal E complex have been ascertained using proteomic and structural methods (Hartmuth et al. 2002, Rappsilber et al. 2002, Hegele et al. 2012, Makarov et al. 2012).

Literature References

PubMed ID	Title	Journal	Year
26420826	Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins Crisci, A, Raleff, F, Bagdiul, I, Raabe, M, Urlaub, H, Rain, JC, Krämer, A	Nucleic Acids Res.	2015
10882114	Functional association of U2 snRNP with the ATP-independent spliceosomal complex E Das, R, Zhou, Z, Reed, R	Mol Cell	2000
25555158	Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5' splice site recognition Kondo, Y, Oubridge, C, van Roon, AM, Nagai, K	Elife	2015
12477934	Protein composition of human prespliceosomes isolated by a tobramycin affinity-selection method. Hartmuth, K, Urlaub, H, Vornlocher, HP, Will, CL, Gentzel, M, Wilm, M, Lührmann, R	Proc Natl Acad Sci U S A	2002
3757028	A compensatory base change in U1 snRNA suppresses a 5' splice site mutation Zhuang, Y, Weiner, AM	Cell	1986
33446560	Structure of a transcribing RNA polymerase II-U1 snRNP complex Zhang, S, Aibara, S, Vos, SM, Agafonov, DE, Lührmann, R, Cramer, P	Science	2021
9512519	A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint region recognition Berglund, JA, Abovich, N, Rosbash, M	Genes Dev	1998
26969736	Noncanonical registers and base pairs in human 5' splice-site selection Tan, J, Ho, JX, Zhong, Z, Luo, S, Chen, G, Roca, X	Nucleic Acids Res	2016
12176931	Large-scale proteomic analysis of the human spliceosome. Rappsilber, J, Ryder, U, Lamond, AI, Mann, M	Genome Res	2002
9016565	Association of U2 snRNP with the spliceosomal complex E Hong, W, Bennett, M, Xiao, Y, Feld Kramer, R, Wang, C, Reed, R	Nucleic Acids Res	1997
22110043	Functional mammalian spliceosomal complex E contains SMN complex proteins in addition to U1 and U2 snRNPs Makarov, EM, Owen, N, Bottrill, A, Makarova, OV	Nucleic Acids Res.	2012
22365833	Dynamic protein-protein interaction wiring of the human spliceosome Hegele, A, Kamburov, A, Grossmann, A, Sourlis, C, Wowro, S, Weimann, M, Will, CL, Pena, V, Lührmann, R, Stelzl, U	Mol. Cell	2012