Reactome | Formation of the Spliceosomal P complex and exon ligation

Formation of the Spliceosomal P complex and exon ligation

Stable Identifier

R-HSA-9770236

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

nucleoplasm

Synonyms

Second catalytic step of mRNA splicing

ReviewStatus

5/5

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Formation of the Spliceosomal P complex and exon ligation

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Two magnesium ions coordinated by 4 phosphate groups of the U6 snRNA in the Spliceosomal C* complex (Bertram et al. 2017, Zhang et al. 2017) catalyze the transesterification reaction between the 3' nucleotide residue of the upstream exon and the 5' nucleotide residue of the downstream exon. The 3' hydroxyl group of the upstream exon nucleophilically attacks the 5' phosphate group of the downstream exon and the magnesium ions stabilize the pentacovalent transition state. Upon completion of exon ligation, the Spliceosomal P complex (post-catalytic complex) is formed. CACTIN, SDE2, NKAP, and PKRIP1 originally present in the Spliceosomal C* complex stabilize the branch helix (Fica et al. 2019, Zhang et al. 2019). FAM32A, not found in yeast, bridges the upstream exon and the 3' splice site of the intron in the Spliceosomal P complex (Fica et al. 2019). An Exon Junction Complex (EJC) is bound to the upstream exon 20-24 nucleotides upstream of the splice site (Zhang and Krainer 2007, Zhang et al. 2019). SRRM2 and CWC22 are also bound to the upstream exon (Zhang et al. 2019). ALYREF, which was initially recruited to the cap binding complex of the early spliceosome, now becomes associated with EJCs and nearby regions on the spliced mRNA (Zhou et al. 2000, Chi et al. 2013). Auxiliary factors, the ASAP complex or the PSAP complex also bind the EJC (Tange et al. 2005). DHX8 (homolog of yeast Prp22) which will dissociate the spliced mRNP from the Intron Lariat Spliceosome is bound to PRPF8 (homolog of yeast Prp8) (Zhang et al. 2019). The components of the Spliceosomal P complex have been ascertained using proteomic and structural methods (Kataoka and Dreyfuss 2004, Ilagan et al. 2013, Fica et al. 2019).

Literature References

PubMed ID	Title	Journal	Year
16314458	Biochemical analysis of the EJC reveals two new factors and a stable tetrameric protein core Tange, TØ, Moore, MJ, Jurica, MS, Shibuya, T	RNA	2005
11014198	The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans Reed, R, Luo, MJ, Katahira, J, Hurt, E, Straesser, K, Zhou, Z	Nature	2000
23222130	Aly and THO are required for assembly of the human TREX complex and association of TREX components with the spliced mRNA Chang, X, Shi, M, Wu, G, Chi, B, Wang, L, Tan, M, Wang, Q, Cheng, H	Nucleic Acids Res.	2013
28076346	Cryo-EM structure of a human spliceosome activated for step 2 of splicing Bertram, K, Will, CL, Lührmann, R, Dybkov, O, Agafonov, DE, Stark, H, Urlaub, H, Kastner, B, Hartmuth, K, Liu, WT	Nature	2017
28502770	An Atomic Structure of the Human Spliceosome Yan, C, Shi, Y, Zhang, X, Finci, LI, Lei, J, Hang, J	Cell	2017
23345524	Rearrangements within human spliceosomes captured after exon ligation Ilagan, JO, Chalkley, RJ, Jurica, MS, Burlingame, AL	RNA	2013
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
30728453	Structures of the human spliceosomes before and after release of the ligated exon Shi, Y, Liu, D, Yan, C, Zhang, W, Zhang, X, Lei, J, Zhan, X	Cell Res	2019
30705154	A human postcatalytic spliceosome structure reveals essential roles of metazoan factors for exon ligation Wilkinson, ME, Fica, SM, Nagai, K, Newman, AJ, Oubridge, C	Science	2019
17606899	Splicing remodels messenger ribonucleoprotein architecture via eIF4A3-dependent and -independent recruitment of exon junction complex components Krainer, AR, Zhang, Z	Proc Natl Acad Sci U S A	2007