Delta14-sterol reductase activity / spliceosomal complex disassembly / U2-type post-mRNA release spliceosomal complex / ergosterol biosynthetic process / spliceosomal snRNP complex / post-mRNA release spliceosomal complex / generation of catalytic spliceosome for first transesterification step / pICln-Sm protein complex / U2-type catalytic step 1 spliceosome / pre-mRNA binding ...Delta14-sterol reductase activity / spliceosomal complex disassembly / U2-type post-mRNA release spliceosomal complex / ergosterol biosynthetic process / spliceosomal snRNP complex / post-mRNA release spliceosomal complex / generation of catalytic spliceosome for first transesterification step / pICln-Sm protein complex / U2-type catalytic step 1 spliceosome / pre-mRNA binding / snRNP binding / small nuclear ribonucleoprotein complex / SMN-Sm protein complex / spliceosomal tri-snRNP complex / U2-type spliceosomal complex / mRNA cis splicing, via spliceosome / U2-type catalytic step 2 spliceosome / U4 snRNP / U2 snRNP / U1 snRNP / U2-type prespliceosome / precatalytic spliceosome / generation of catalytic spliceosome for second transesterification step / spliceosomal complex assembly / protein K63-linked ubiquitination / Prp19 complex / U5 snRNP / U6 snRNA binding / spliceosomal snRNP assembly / U4/U6 x U5 tri-snRNP complex / catalytic step 2 spliceosome / RNA splicing / peptidyl-prolyl cis-trans isomerase activity / RNA polymerase II CTD heptapeptide repeat P3 isomerase activity / RNA polymerase II CTD heptapeptide repeat P6 isomerase activity / helicase activity / peptidylprolyl isomerase / spliceosomal complex / RING-type E3 ubiquitin transferase / mRNA splicing, via spliceosome / mRNA processing / ubiquitin protein ligase activity / protein folding / hydrolase activity / RNA helicase / DNA repair / mRNA binding / endoplasmic reticulum membrane / DNA binding / RNA binding / ATP binding / nucleus / metal ion binding / cytosol / cytoplasm Similarity search - Function
Tetratricopeptide repeat / Sterol biosynthesis ERG24/DHCR-like / Sterol reductase, conserved site / Ergosterol biosynthesis ERG4/ERG24 family / Sterol reductase family signature 1. / Sterol reductase family signature 2. / mRNA splicing factor Cwf18-like / : / cwf18 pre-mRNA splicing factor / Nineteen complex-related protein 2 ...Tetratricopeptide repeat / Sterol biosynthesis ERG24/DHCR-like / Sterol reductase, conserved site / Ergosterol biosynthesis ERG4/ERG24 family / Sterol reductase family signature 1. / Sterol reductase family signature 2. / mRNA splicing factor Cwf18-like / : / cwf18 pre-mRNA splicing factor / Nineteen complex-related protein 2 / Pre-mRNA-splicing factor Isy1 / Pre-mRNA-splicing factor Isy1 superfamily / Isy1-like splicing family / cwf21 / Slt11, RNA recognition motif / Pre-mRNA-splicing factor Cwc2, RNA recognition motif / : / : / Intron-binding protein aquarius, beta-barrel / Intron-binding protein aquarius insert domain / Pre-mRNA-splicing factor SPF27 / Torus domain / Breast carcinoma amplified sequence 2 (BCAS2) / Torus domain / CWF11 family / Intron-binding protein aquarius, N-terminal / Intron-binding protein aquarius N-terminal / mRNA splicing factor SYF2 / SYF2 splicing factor / Helix hairpin bin domain superfamily / : / : / mRNA splicing factor Cwf21 domain / cwf21 domain / Pre-mRNA-processing factor 17 / HAT (Half-A-TPR) repeat / Myb-like domain profile. / Pre-mRNA-splicing factor 19 / Pre-mRNA-processing factor 19 / Prp19/Pso4-like / Cyclophilin-type peptidyl-prolyl cis-trans isomerase, cyclophilin A-like / BUD31/G10-related, conserved site / G10 protein signature 1. / : / DNA2/NAM7 helicase, helicase domain / : / AAA domain / STL11, N-terminal / SKI-interacting protein SKIP, SNW domain / SKI-interacting protein, SKIP / SKIP/SNW domain / Pre-mRNA-splicing factor Cwf15/Cwc15 / Suppressor of forked / Cwf15/Cwc15 cell cycle control protein / Suppressor of forked protein (Suf) / WD repeat Prp46/PLRG1-like / Pre-mRNA-splicing factor Cwc2/Slt11 / : / G10 protein / Pre-mRNA-splicing factor BUD31 / Pre-mRNA splicing factor component Cdc5p/Cef1, C-terminal / : / : / pre-mRNA splicing factor component / DNA2/NAM7-like helicase / : / Initiation factor eIF-4 gamma, MA3 / MA3 domain / MI domain profile. / Domain in DAP-5, eIF4G, MA-3 and other proteins. / MIF4G domain / Myb-like DNA-binding domain / Middle domain of eukaryotic initiation factor 4G (eIF4G) / MIF4G-like, type 3 / Small nuclear ribonucleoprotein D1 / U-box domain profile. / Modified RING finger domain / U-box domain / Zinc finger, CCCH-type superfamily / : / Helicase associated domain (HA2), ratchet-like / Pre-mRNA-splicing factor Syf1-like / DEAD-box helicase, OB fold / Oligonucleotide/oligosaccharide-binding (OB)-fold / Helicase associated domain (HA2), winged-helix / Helicase-associated domain / Helicase associated domain (HA2) Add an annotation / Anaphase-promoting complex subunit 4, WD40 domain / Small nuclear ribonucleoprotein Sm D3 / Small nuclear ribonucleoprotein Sm D2 / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein G / Small nuclear ribonucleoprotein F / Anaphase-promoting complex subunit 4 WD40 domain / Sm-like protein Lsm7/SmG / Like-Sm (LSM) domain containing protein, LSm4/SmD1/SmD3 / Zinc finger, CCCH-type / Zinc finger C3H1-type profile. / Sm-like protein Lsm6/SmF / Myb-type HTH DNA-binding domain profile. Similarity search - Domain/homology
Sm protein F / Putative pre-mRNA splicing protein / RNA helicase / Small nuclear ribonucleoprotein Sm D1 / Putative pre-mRNA splicing protein / Pre-mRNA-splicing factor PRP46 / Suppressor of forked domain-containing protein / Peptidyl-prolyl cis-trans isomerase / Uncharacterized protein / Delta(14)-sterol reductase ...Sm protein F / Putative pre-mRNA splicing protein / RNA helicase / Small nuclear ribonucleoprotein Sm D1 / Putative pre-mRNA splicing protein / Pre-mRNA-splicing factor PRP46 / Suppressor of forked domain-containing protein / Peptidyl-prolyl cis-trans isomerase / Uncharacterized protein / Delta(14)-sterol reductase / Putative pre-mRNA splicing protein / Putative bud site selection protein / Pre-mRNA-splicing factor SYF2 / Putative pre-mRNA splicing protein / Putative pre-mRNA splicing protein / Putative pre-mRNA splicing protein / Putative pre-mRNA splicing protein / Putative pre-mRNA splicing protein / Small nuclear ribonucleoprotein E / Anaphase-promoting complex subunit 4-like WD40 domain-containing 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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