登録情報 データベース : EMDB / ID : EMD-19399 ダウンロードとリンクタイトル Integrative Structure of the human intron lariat Spliceosome (ILS'') マップデータcomposite map 詳細 試料複合体 : Human Intron-lariat splicoesomeRNA : x 4種タンパク質・ペプチド : x 33種リガンド : x 3種 詳細 キーワード mRNA / splicing / intron lariat spliceosome / pre-mRNA機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
RNA lariat debranching enzyme activator activity / spliceosomal complex disassembly / post-spliceosomal complex / negative regulation of double-strand break repair via nonhomologous end joining / biomineral tissue development / U2-type post-mRNA release spliceosomal complex / protection from non-homologous end joining at telomere / regulation of skeletal muscle satellite cell proliferation / positive regulation of myoblast proliferation / regulation of retinoic acid receptor signaling pathway ... RNA lariat debranching enzyme activator activity / spliceosomal complex disassembly / post-spliceosomal complex / negative regulation of double-strand break repair via nonhomologous end joining / biomineral tissue development / U2-type post-mRNA release spliceosomal complex / protection from non-homologous end joining at telomere / regulation of skeletal muscle satellite cell proliferation / positive regulation of myoblast proliferation / regulation of retinoic acid receptor signaling pathway / post-mRNA release spliceosomal complex / U2 snRNP binding / U7 snRNA binding / histone pre-mRNA DCP binding / U7 snRNP / 3'-5' RNA helicase activity / endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / generation of catalytic spliceosome for first transesterification step / histone methyltransferase binding / histone pre-mRNA 3'end processing complex / alternative mRNA splicing, via spliceosome / regulation of vitamin D receptor signaling pathway / SLBP independent Processing of Histone Pre-mRNAs / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / nuclear retinoic acid receptor binding / embryonic brain development / protein methylation / U12-type spliceosomal complex / 7-methylguanosine cap hypermethylation / U1 snRNP binding / RNA splicing, via transesterification reactions / mRNA 3'-end processing / sno(s)RNA-containing ribonucleoprotein complex / methylosome / ATP-dependent activity, acting on RNA / pICln-Sm protein complex / oocyte development / U2-type catalytic step 1 spliceosome / positive regulation of mRNA splicing, via spliceosome / pre-mRNA binding / snRNP binding / small nuclear ribonucleoprotein complex / response to alkaloid / telomerase holoenzyme complex / SMN-Sm protein complex / P granule / telomerase RNA binding / spliceosomal tri-snRNP complex / positive regulation by host of viral transcription / U2-type precatalytic spliceosome / U2-type spliceosomal complex / positive regulation of vitamin D receptor signaling pathway / commitment complex / mRNA cis splicing, via spliceosome / U2-type prespliceosome assembly / Transport of Mature mRNA derived from an Intron-Containing Transcript / nuclear vitamin D receptor binding / Notch binding / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / U2-type catalytic step 2 spliceosome / RUNX3 regulates NOTCH signaling / NOTCH4 Intracellular Domain Regulates Transcription / U4 snRNP / U2 snRNP / RNA Polymerase II Transcription Termination / U1 snRNP / NOTCH3 Intracellular Domain Regulates Transcription / U2-type prespliceosome / WD40-repeat domain binding / protein peptidyl-prolyl isomerization / inner cell mass cell proliferation / positive regulation of neurogenesis / ubiquitin-ubiquitin ligase activity / snoRNA binding / nuclear androgen receptor binding / K63-linked polyubiquitin modification-dependent protein binding / precatalytic spliceosome / lipid biosynthetic process / muscle organ development / generation of catalytic spliceosome for second transesterification step / Notch-HLH transcription pathway / Formation of paraxial mesoderm / positive regulation of transforming growth factor beta receptor signaling pathway / SMAD binding / spliceosomal complex assembly / mitotic G2 DNA damage checkpoint signaling / mRNA Splicing - Minor Pathway / mRNA 3'-splice site recognition / spliceosomal tri-snRNP complex assembly / blastocyst development / Prp19 complex / protein K63-linked ubiquitination / U5 snRNA binding / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / protein localization to nucleus / U5 snRNP / positive regulation of G1/S transition of mitotic cell cycle / embryonic organ development / U2 snRNA binding / U6 snRNA binding 類似検索 - 分子機能 Intron Large complex component GCFC2-like / Septin and tuftelin interacting protein / Nuclear protein DGCR14/ESS-2 / Tuftelin interacting protein, N-terminal domain / : / Nuclear protein Es2 / Tuftelin interacting protein N terminal / Vertebrate Splicing regulator sde2, N-terminal ubiquitin domain / GCF, C-terminal / GC-rich sequence DNA-binding factor-like protein ... Intron Large complex component GCFC2-like / Septin and tuftelin interacting protein / Nuclear protein DGCR14/ESS-2 / Tuftelin interacting protein, N-terminal domain / : / Nuclear protein Es2 / Tuftelin interacting protein N terminal / Vertebrate Splicing regulator sde2, N-terminal ubiquitin domain / GCF, C-terminal / GC-rich sequence DNA-binding factor-like protein / mRNA splicing factor Cwf18-like / TFP11/STIP/Ntr1 / : / cwf18 pre-mRNA splicing factor / Splicing regulator SDE2, SDE2 domain / Cwf19-like protein, C-terminal domain-2 / Cwf19-like, C-terminal domain-1 / Cwf19-like protein / Protein similar to CwfJ C-terminus 2 / Protein similar to CwfJ C-terminus 1 / DHX15, DEXH-box helicase domain / Pre-mRNA-splicing factor Isy1 / Pre-mRNA-splicing factor Isy1 superfamily / Isy1-like splicing family / Prp19 WD40 domain / : / : / Intron-binding protein aquarius, beta-barrel / Intron-binding protein aquarius insert domain / Pre-mRNA-splicing factor SPF27 / Breast carcinoma amplified sequence 2 (BCAS2) / 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 / : / Replication stress response SDE2 C-terminal / G-patch domain / G-patch domain profile. / G-patch domain / glycine rich nucleic binding domain / Pre-mRNA-processing factor 17 / U-box domain / : / : / : / Pre-mRNA-splicing factor SYF1 middle HAT repeat / Pre-mRNA-splicing factor 19 / Pre-mRNA-processing factor 19 / Prp19/Pso4-like / G10 protein signature 2. / Cyclophilin-type peptidyl-prolyl cis-trans isomerase, cyclophilin A-like / BUD31/G10-related, conserved site / G10 protein signature 1. / : / Pre-mRNA-splicing factor Syf1/CRNKL1 C-terminal HAT repeat / DNA2/NAM7 helicase, helicase domain / : / AAA domain / STL11, N-terminal / : / Pre-mRNA-splicing factor Syf1/CNRKL1 N-terminal HAT repeat / SKI-interacting protein SKIP, SNW domain / SKI-interacting protein, SKIP / SKIP/SNW domain / Pre-mRNA-splicing factor Cwf15/Cwc15 / Cwf15/Cwc15 cell cycle control protein / 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 / : / Small ribonucleoprotein associated, SmB/SmN / Myb-like DNA-binding domain / Small nuclear ribonucleoprotein D1 / U-box domain profile. / HIT-like superfamily / Modified RING finger domain / U-box domain / Zinc finger, CCCH-type superfamily / zinc finger / 116kDa U5 small nuclear ribonucleoprotein component, N-terminal / 116kDa U5 small nuclear ribonucleoprotein component, C-terminal / Snu114, GTP-binding domain / 116 kDa U5 small nuclear ribonucleoprotein component N-terminus / Pre-mRNA-splicing factor Syf1-like / : / Helicase associated domain (HA2), ratchet-like / DEAD-box helicase, OB fold / Oligonucleotide/oligosaccharide-binding (OB)-fold / Helicase associated domain (HA2), winged-helix / Helicase-associated domain 類似検索 - ドメイン・相同性 ATP-dependent RNA helicase DHX15 / Pleiotropic regulator 1 / RNA helicase aquarius / Pre-mRNA-processing factor 17 / Pre-mRNA-splicing factor SPF27 / Pre-mRNA-splicing factor SYF2 / Small nuclear ribonucleoprotein-associated proteins B and B' / Protein BUD31 homolog / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein F ... ATP-dependent RNA helicase DHX15 / Pleiotropic regulator 1 / RNA helicase aquarius / Pre-mRNA-processing factor 17 / Pre-mRNA-splicing factor SPF27 / Pre-mRNA-splicing factor SYF2 / Small nuclear ribonucleoprotein-associated proteins B and B' / Protein BUD31 homolog / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein F / Small nuclear ribonucleoprotein G / Small nuclear ribonucleoprotein Sm D1 / Small nuclear ribonucleoprotein Sm D2 / Small nuclear ribonucleoprotein Sm D3 / SNW domain-containing protein 1 / 116 kDa U5 small nuclear ribonucleoprotein component / CWF19-like protein 2 / CWF19-like protein 1 / Splicing regulator SDE2 / Pre-mRNA-processing-splicing factor 8 / Coiled-coil domain-containing protein 12 / Splicing factor ESS-2 homolog / U5 small nuclear ribonucleoprotein 40 kDa protein / Cell division cycle 5-like protein / Crooked neck-like protein 1 / Pre-mRNA-splicing factor SYF1 / Pre-mRNA-splicing factor RBM22 / Spliceosome-associated protein CWC15 homolog / Tuftelin-interacting protein 11 / Pre-mRNA-splicing factor ISY1 homolog / Pre-mRNA-processing factor 19 / Peptidyl-prolyl cis-trans isomerase-like 1 / PAX3- and PAX7-binding protein 1 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.5 Å 詳細 データ登録者Rothe P / Vorlaender MK / Plaschka C 資金援助 European Union, 1件 詳細 詳細を隠すOrganization Grant number 国 European Research Council (ERC) European Union
引用ジャーナル : Nature / 年 : 2024タイトル : Mechanism for the initiation of spliceosome disassembly.著者 : Matthias K Vorländer / Patricia Rothe / Justus Kleifeld / Eric D Cormack / Lalitha Veleti / Daria Riabov-Bassat / Laura Fin / Alex W Phillips / Luisa Cochella / Clemens Plaschka / 要旨 : Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on ... Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on spliceosome assembly and remodelling for catalysis, but the mechanism of disassembly remains unclear. Here we report cryo-electron microscopy structures of nematode and human terminal intron lariat spliceosomes along with biochemical and genetic data. Our results uncover how four disassembly factors and the conserved RNA helicase DHX15 initiate spliceosome disassembly. The disassembly factors probe large inner and outer spliceosome surfaces to detect the release of ligated mRNA. Two of these factors, TFIP11 and C19L1, and three general spliceosome subunits, SYF1, SYF2 and SDE2, then dock and activate DHX15 on the catalytic U6 snRNA to initiate disassembly. U6 therefore controls both the start and end of pre-mRNA splicing. Taken together, our results explain the molecular basis of the initiation of canonical spliceosome disassembly and provide a framework to understand general spliceosomal RNA helicase control and the discard of aberrant spliceosomes. 履歴 登録 2024年1月11日 - ヘッダ(付随情報) 公開 2024年9月18日 - マップ公開 2024年9月18日 - 更新 2024年10月16日 - 現状 2024年10月16日 処理サイト : PDBe / 状態 : 公開
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