Delta14-sterol reductase activity / U2-type post-mRNA release spliceosomal complex / spliceosomal snRNP complex / spliceosomal complex disassembly / ergosterol biosynthetic process / generation of catalytic spliceosome for first transesterification step / nuclear lumen / pICln-Sm protein complex / snRNP binding / SMN-Sm protein complex ...Delta14-sterol reductase activity / U2-type post-mRNA release spliceosomal complex / spliceosomal snRNP complex / spliceosomal complex disassembly / ergosterol biosynthetic process / generation of catalytic spliceosome for first transesterification step / nuclear lumen / pICln-Sm protein complex / snRNP binding / SMN-Sm protein complex / spliceosomal tri-snRNP complex / post-mRNA release spliceosomal complex / U2-type spliceosomal complex / pre-mRNA binding / U2-type catalytic step 2 spliceosome / U1 snRNP / U2 snRNP / U4 snRNP / U2-type prespliceosome / U2-type catalytic step 1 spliceosome / generation of catalytic spliceosome for second transesterification step / spliceosomal complex assembly / precatalytic spliceosome / Prp19 complex / U5 snRNP / U6 snRNA binding / mRNA cis splicing, via spliceosome / U4/U6 x U5 tri-snRNP complex / spliceosomal snRNP assembly / catalytic step 2 spliceosome / protein K63-linked ubiquitination / helicase activity / mRNA processing / spliceosomal complex / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / mRNA splicing, via spliceosome / RING-type E3 ubiquitin transferase / regulation of gene expression / ubiquitin protein ligase activity / protein folding / RNA helicase activity / RNA helicase / mRNA binding / endoplasmic reticulum membrane / metal ion binding / RNA binding / ATP binding / nucleus / cytosol / cytoplasm Similarity search - Function
Sterol biosynthesis ERG24/DHCR-like / Sterol reductase, conserved site / Ergosterol biosynthesis ERG4/ERG24 family / Sterol reductase family signature 1. / Sterol reductase family signature 2. / : / Nineteen complex-related protein 2 / mRNA splicing factor Cwf18-like / cwf18 pre-mRNA splicing factor / : ...Sterol biosynthesis ERG24/DHCR-like / Sterol reductase, conserved site / Ergosterol biosynthesis ERG4/ERG24 family / Sterol reductase family signature 1. / Sterol reductase family signature 2. / : / Nineteen complex-related protein 2 / mRNA splicing factor Cwf18-like / cwf18 pre-mRNA splicing factor / : / PRP39 C-terminal HAT repeat / cwf21 / Pre-mRNA-splicing factor Isy1 / Slt11, RNA recognition motif / Pre-mRNA-splicing factor Isy1 superfamily / Isy1-like splicing family / Pre-mRNA-splicing factor Cwc2, RNA recognition motif / Torus domain / Torus domain / : / : / Intron-binding protein aquarius, beta-barrel / Intron-binding protein aquarius insert domain / Pre-mRNA-splicing factor SPF27 / Breast carcinoma amplified sequence 2 (BCAS2) / mRNA splicing factor SYF2 / SYF2 splicing factor / CWF11 family / Intron-binding protein aquarius, N-terminal / Intron-binding protein aquarius N-terminal / Helix hairpin bin domain superfamily / : / : / cwf21 domain / mRNA splicing factor Cwf21 domain / Pre-mRNA-processing factor 17 / : / Pre-mRNA-splicing factor SYF1 middle HAT repeat / Pre-mRNA-splicing factor 19 / Pre-mRNA-processing factor 19 / : / : / Prp19/Pso4-like / BUD31/G10-related, conserved site / G10 protein signature 1. / : / STL11, N-terminal / Cyclophilin-type peptidyl-prolyl cis-trans isomerase, cyclophilin A-like / Myb-like domain profile. / : / Pre-mRNA-splicing factor Syf1/CRNKL1 C-terminal HAT repeat / Pre-mRNA-splicing factor Cwc2/Slt11 / SKI-interacting protein SKIP, SNW domain / Pre-mRNA-splicing factor Cwf15/Cwc15 / SKI-interacting protein, SKIP / SKIP/SNW domain / Cwf15/Cwc15 cell cycle control protein / PRP39 N-terminal HAT repeat / WD repeat Prp46/PLRG1-like / Pre-mRNA splicing factor component Cdc5p/Cef1, C-terminal / : / pre-mRNA splicing factor component / G10 protein / : / Pre-mRNA-splicing factor BUD31 / Initiation factor eIF-4 gamma, MA3 / : / : / MA3 domain / Pre-mRNA-splicing factor Syf1/CNRKL1 N-terminal HAT repeat / MI domain profile. / Domain in DAP-5, eIF4G, MA-3 and other proteins. / Anaphase-promoting complex subunit 4, WD40 domain / DNA2/NAM7 helicase, helicase domain / AAA domain / MIF4G domain / Myb-like DNA-binding domain / DNA2/NAM7-like helicase / : / Anaphase-promoting complex subunit 4 WD40 domain / Middle domain of eukaryotic initiation factor 4G (eIF4G) / MIF4G-like, type 3 / Small nuclear ribonucleoprotein D1 / Zinc finger, CCCH-type superfamily / U-box domain profile. / Pre-mRNA-splicing factor Syf1-like / Modified RING finger domain / U-box domain / Small nuclear ribonucleoprotein Sm D2 / Small nuclear ribonucleoprotein Sm D3 / Small nuclear ribonucleoprotein G / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein F / : / Nucleolar protein 10-like, N-terminal domain / : / Helicase associated domain (HA2), ratchet-like / DEAD-box helicase, OB fold / Helicase associated domain (HA2), winged-helix / Oligonucleotide/oligosaccharide-binding (OB)-fold Similarity search - Domain/homology
Sm protein F / Pre-mRNA splicing protein / RNA helicase / Small nuclear ribonucleoprotein Sm D1 / Pre-mRNA splicing protein / Pre-mRNA-splicing factor PRP46 / Pre-mRNA splicing protein / Peptidyl-prolyl cis-trans isomerase / Uncharacterized protein / Delta(14)-sterol reductase ...Sm protein F / Pre-mRNA splicing protein / RNA helicase / Small nuclear ribonucleoprotein Sm D1 / Pre-mRNA splicing protein / Pre-mRNA-splicing factor PRP46 / Pre-mRNA splicing protein / Peptidyl-prolyl cis-trans isomerase / Uncharacterized protein / Delta(14)-sterol reductase / Pre-mRNA splicing protein / Bud site selection protein / Pre-mRNA-splicing factor SYF2 / Pre-mRNA-splicing factor CWC22 / Pre-mRNA-splicing factor SYF1 / Pre-mRNA splicing protein / Pre-mRNA-splicing factor CWC2 / Pre-mRNA splicing protein / Small nuclear ribonucleoprotein E / Uncharacterized protein / Uncharacterized protein / Pre-mRNA-splicing factor SPF27 / Pre-mRNA-processing protein 45 / Pre-mRNA-splicing factor / Pre-mRNA-processing factor 19 / Small nuclear ribonucleoprotein Sm D3 / Sm protein B / Small nuclear ribonucleoprotein G / Nineteen complex-related protein 2-domain-containing protein Similarity search - Component
Journal: Cell Res / Year: 2025 Title: Structural insights into spliceosome fidelity: DHX35-GPATCH1- mediated rejection of aberrant splicing substrates. Authors: Yi Li / Paulina Fischer / Mengjiao Wang / Qianxing Zhou / Aixia Song / Rui Yuan / Wanyu Meng / Fei Xavier Chen / Reinhard Lührmann / Benjamin Lau / Ed Hurt / Jingdong Cheng / Abstract: The spliceosome, a highly dynamic macromolecular assembly, catalyzes the precise removal of introns from pre-mRNAs. Recent studies have provided comprehensive structural insights into the step-wise ...The spliceosome, a highly dynamic macromolecular assembly, catalyzes the precise removal of introns from pre-mRNAs. Recent studies have provided comprehensive structural insights into the step-wise assembly, catalytic splicing and final disassembly of the spliceosome. However, the molecular details of how the spliceosome recognizes and rejects suboptimal splicing substrates remained unclear. Here, we show cryo-electron microscopy structures of spliceosomal quality control complexes from a thermophilic eukaryote, Chaetomium thermophilum. The spliceosomes, henceforth termed B*, are stalled at a catalytically activated state but prior to the first splicing reaction due to an aberrant 5' splice site conformation. This state is recognized by G-patch protein GPATCH1, which is docked onto PRP8-EN and -RH domains and has recruited the cognate DHX35 helicase to its U2 snRNA substrate. In B*, DHX35 has dissociated the U2/branch site helix, while the disassembly helicase DHX15 is docked close to its U6 RNA 3'-end substrate. Our work thus provides mechanistic insights into the concerted action of two spliceosomal helicases in maintaining splicing fidelity by priming spliceosomes that are bound to aberrant splice substrates for disassembly.
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