module: dmel_spliceosome title: Major (U2-type) spliceosome in Drosophila melanogaster label: Spliceosome module_type: PROTEIN_COMPLEX description: >- The major spliceosome removes U2-type introns from nuclear pre-mRNAs. It is assembled stepwise on each intron from the U1, U2, U4/U6 and U5 small nuclear ribonucleoprotein particles (snRNPs) and many non-snRNP proteins. Each snRNP contains a small nuclear RNA; the U1, U2, U4 and U5 snRNAs carry a heptameric ring of Sm proteins, whereas U6 snRNA binds the related LSm proteins. U1 snRNP recognizes the 5' splice site, and the U2 snRNP auxiliary factor (U2AF) together with SF1 recognizes the 3' splice site region, allowing U2 snRNP to pair with the branch site (complex A). Joining of the U4/U6.U5 tri-snRNP forms the precatalytic complex B; release of U1 and U4 and recruitment of the Prp19 complex and associated proteins create the catalytic spliceosome, which carries out the two transesterification steps (complex C) and then releases the spliced mRNA (post-catalytic complex P) with an exon junction complex deposited upstream of the exon-exon junction. summary: >- snRNPs, U2AF and stage-specific non-snRNP proteins that assemble on U2-type introns and catalyse pre-mRNA splicing. concepts: - {id: GO:0005681, label: spliceosomal complex} cellular_components: - {id: GO:0005654, label: nucleoplasm} processes: - {id: GO:0000398, label: "mRNA splicing, via spliceosome"} parts: - id: sm_rings label: Sm protein rings role: snRNA-binding Sm heptamers description: >- Seven Sm proteins form the ring assembled on the Sm site of the U1, U2, U4 and U5 snRNAs. FlyBase also groups a U7-type Sm ring in which Lsm10 and Lsm11 replace SmD1 and SmD2; the U7 snRNP acts in histone pre-mRNA 3' end processing rather than in splicing. variant_sets: - id: sm_ring_variants label: Spliceosomal or U7 Sm ring selection: ONE_OR_MORE variants: - id: spliceosomal_sm_ring label: Spliceosomal Sm ring group: SM complex_term: {id: GO:0120114, label: Sm-like protein family complex} - id: u7_sm_ring label: U7 snRNP Sm ring group: U7-SM complex_term: {id: GO:0120114, label: Sm-like protein family complex} - id: snrnps label: Spliceosomal snRNPs role: snRNA-protein particles that form the catalytic core description: >- The U1, U2, U4/U6 and U5 snRNPs and the U4/U6.U5 tri-snRNP, each listed with its snRNA genes and its protein components as grouped by FlyBase. parts: - id: u1_snrnp label: U1 snRNP role: 5' splice site recognition group: U1 complex_term: {id: GO:0005685, label: U1 snRNP} - id: u2_snrnp label: U2 snRNP role: branch site recognition (includes SF3a and SF3b) group: U2 complex_term: {id: GO:0005686, label: U2 snRNP} - id: u4_u6_snrnp label: U4/U6 di-snRNP role: U6 snRNA delivery in base-paired U4/U6 form group: U4-U6 complex_term: {id: GO:0071001, label: U4/U6 snRNP} - id: u5_snrnp label: U5 snRNP role: exon alignment and spliceosome remodelling (Prp8, Brr2) group: U5 complex_term: {id: GO:0005682, label: U5 snRNP} - id: tri_snrnp label: U4/U6.U5 tri-snRNP role: preassembled particle that joins complex A to form complex B group: U4-U6-U5 complex_term: {id: GO:0046540, label: U4/U6 x U5 tri-snRNP complex} connections: - source: u4_u6_snrnp target: tri_snrnp connection_type: PROVIDES_INPUT_FOR description: U4/U6 di-snRNP associates with U5 snRNP to form the tri-snRNP. - source: u5_snrnp target: tri_snrnp connection_type: PROVIDES_INPUT_FOR description: U5 snRNP associates with U4/U6 to form the tri-snRNP. - id: u2af label: U2 snRNP auxiliary factor role: 3' splice site and polypyrimidine tract recognition group: U2AF complex_term: {id: GO:0089701, label: U2AF complex} - id: complex_a_factors label: Complex A non-snRNP factors role: early intron recognition and A-complex assembly description: >- Non-snRNP proteins that FlyBase lists in spliceosome complex A, beyond the U1 and U2 snRNPs and U2AF: the branch point binding protein SF1, the DEAD-box helicase Prp5, U2-associated proteins (Spf30, Spf45, CG9346, CG31550), RBM5-like proteins, hnRNPs and the DHX15 helicase. genes: [CG31550, CG4887, CG4896, CG9346, Dhx15, Hrb87F, Hrb98DE, Prp5, SF1, Spf30, Spf45, hfp, scaf6, sqd] - id: complex_b_factors label: Complex B and Bact non-snRNP factors role: precatalytic spliceosome assembly and activation description: >- Proteins that FlyBase lists in spliceosome complex B but not in complex A or the snRNPs. They include the Prp19 complex (NTC) and NTC-related proteins that are recruited during activation and stay through the catalytic stages, and B-specific proteins such as Prp38, Smu1 and Mfap1. parts: - id: prp19_complex_core label: Prp19 complex (NTC) core role: spliceosome activation and catalytic-core stabilization genes: [Prp19, Cdc5, Tango4, BCAS2] complex_term: {id: GO:0000974, label: Prp19 complex} - id: other_complex_b_factors label: Other complex B factors role: B-complex and Bact-complex proteins genes: [Bx42, CG11586, CG11964, CG14641, CG2685, CG4291, CG9667, Cypl, Mfap1, Ppil4, Prp38, Smu1, beag, c12.1, crn, cyp33, fand, l(1)10Bb, salsa, sip1] - id: complex_c_factors label: Complex C and P non-snRNP factors role: catalytic steps, exon ligation and mRNA release description: >- Proteins that FlyBase lists in the catalytic complex C (and, except Bin1, CG10466, CG3225, CG8833 and Prp18, also in the post-catalytic complex P) but not in earlier complexes. These include second-step factors (Prp18, Slu7), the DEAH-box helicases Prp16 (l(2)37Cb), Prp22 (pea) and abs, and the exon junction complex core deposited during splicing. parts: - id: exon_junction_complex label: Exon junction complex core role: marks spliced exon-exon junctions on the mRNA genes: [CG7483, mago, tsu] complex_term: {id: GO:0035145, label: exon-exon junction complex} - id: other_complex_c_factors label: Other complex C and P factors role: step 1 and step 2 catalytic-stage proteins genes: [Bin1, CG10466, CG10907, CG11777, CG11839, CG12259, CG12343, CG12818, CG13625, CG15432, CG15525, CG16865, CG16890, CG17168, CG3225, CG3511, CG4935, CG5986, CG6015, CG6179, CG7974, CG8833, Cdc2rk, Es2, Gpkow, Hsc70-1, Prp18, Slu7, abs, cactin, l(2)37Cb, mdlc, ncm, pea] connections: - source: snrnps target: complex_a_factors connection_type: PRECEDES description: U1 and U2 snRNPs and U2AF define the intron, forming complex A. - source: complex_a_factors target: complex_b_factors connection_type: PRECEDES description: Tri-snRNP joining converts complex A into complex B, which is activated with NTC recruitment. - source: complex_b_factors target: complex_c_factors connection_type: PRECEDES description: The activated spliceosome carries out branching (complex C) and exon ligation (complex P). notes: >- Decomposition. FlyBase splits the spliceosome two ways: by snRNP (U1, U2, U4-U6, U5, U4-U6-U5) and by assembly stage (SPL-C-A, SPL-C-B, SPL-C-C, SLP-C-P), with the snRNP genes re-listed in each stage group. Here the snRNPs, the Sm rings and U2AF are parts, and each stage part contains only the non-snRNP proteins first listed at that stage (complex A, then B, then C). Complex P adds no protein absent from complex C; it lacks Bin1, CG10466, CG3225, CG8833 and Prp18. Assignment of the NTC core (Prp19, Cdc5, Tango4 [PLRG1], BCAS2) and EJC core (mago, tsu [Y14], CG7483 [eIF4AIII]) follows orthology to the human complexes; other stage factors are kept as stage sets without finer sub-structure. Lsm10 and Lsm11 enter through FlyBase's Sm protein group (U7-SM) and appear only in the U7 Sm ring variant; the U7 snRNP itself (with snRNA:U7) belongs to dmel_histone_mrna_3prime_processing, and the 7SK snRNP, a sibling in FlyBase's snRNP group, to dmel_rnapii_elongation_complexes. The minor (U12-type) spliceosome and splicing regulators (SR proteins, other hnRNPs) are outside this module unless FlyBase lists them in a spliceosome stage. groups: [SPL-C, SM-ALL] function_note: >- No molecular function is assigned in this version. The catalytic centre of the spliceosome is formed by the U2 and U6 snRNAs, and this generated decomposition models snRNP and assembly-stage membership only; the enzymatic protein subunits (for example the DExD/H-box helicases such as Brr2 and Prp5, the Prp19 ubiquitin ligase and the cyclophilins) are not yet given annoton functions.