- EMDB-34841: The cryo-EM structure of human pre-17S U2 snRNP -
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Basic information
Entry
Database: EMDB / ID: EMD-34841
Title
The cryo-EM structure of human pre-17S U2 snRNP
Map data
Sample
Complex: The human pre-17S U2 snRNP
RNA: x 1 types
Protein or peptide: x 20 types
Ligand: x 2 types
Keywords
DDX42 / U2 snRNP / spliceosome / SPLICING
Function / homology
Function and homology information
U2 snRNP binding / U7 snRNA binding / histone pre-mRNA DCP binding / U7 snRNP / histone pre-mRNA 3'end processing complex / U4atac snRNP / SLBP independent Processing of Histone Pre-mRNAs / nuclear histone mRNA catabolic process / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / U4atac/U6atac snRNP ...U2 snRNP binding / U7 snRNA binding / histone pre-mRNA DCP binding / U7 snRNP / histone pre-mRNA 3'end processing complex / U4atac snRNP / SLBP independent Processing of Histone Pre-mRNAs / nuclear histone mRNA catabolic process / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / U4atac/U6atac snRNP / B-WICH complex / U11/U12 snRNP / U4atac/U6atac x U5 tri-snRNP complex / 7-methylguanosine cap hypermethylation / U12-type spliceosomal complex / U1 snRNP binding / RNA splicing, via transesterification reactions / pICln-Sm protein complex / snRNP binding / RNA Polymerase II Transcription Termination / methylosome / splicing factor binding / small nuclear ribonucleoprotein complex / U12-type catalytic step 2 spliceosome / post-spliceosomal complex / protein localization to site of double-strand break / SMN-Sm protein complex / spliceosomal tri-snRNP complex / U12-type precatalytic spliceosome / P granule / commitment complex / U2-type precatalytic spliceosome / poly-ADP-D-ribose modification-dependent protein binding / post-mRNA release spliceosomal complex / U2-type spliceosomal complex / telomerase holoenzyme complex / U2-type prespliceosome assembly / telomerase RNA binding / pre-mRNA binding / U4/U6 snRNP / U2-type catalytic step 2 spliceosome / SAGA complex / U1 snRNP / protein methylation / spliceosome conformational change to release U4 (or U4atac) and U1 (or U11) / U2 snRNP / chromatin-protein adaptor activity / U4 snRNP / U2-type prespliceosome / U2-type catalytic step 1 spliceosome / regulation of RNA splicing / mRNA 3'-splice site recognition / positive regulation of transcription by RNA polymerase III / mRNA Splicing - Minor Pathway / spliceosomal complex assembly / positive regulation of transcription by RNA polymerase I / precatalytic spliceosome / U2 snRNA binding / negative regulation of mRNA splicing, via spliceosome / spliceosomal tri-snRNP complex assembly / U5 snRNP / U1 snRNA binding / RNA splicing / mRNA cis splicing, via spliceosome / U4/U6 x U5 tri-snRNP complex / Cajal body / spliceosomal snRNP assembly / stem cell differentiation / catalytic step 2 spliceosome / mRNA Splicing - Major Pathway / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / regulation of DNA repair / mRNA processing / spliceosomal complex / positive regulation of neuron projection development / negative regulation of protein catabolic process / CHD1 and CHD2 subfamily / mRNA splicing, via spliceosome / double-strand break repair via homologous recombination / B-WICH complex positively regulates rRNA expression / intracellular protein localization / nuclear matrix / mRNA Polyadenylation / site of double-strand break / Dengue Virus-Host Interactions / snRNP Assembly / spermatogenesis / SARS-CoV-2 modulates host translation machinery / nuclear body / regulation of apoptotic process / RNA helicase activity / nuclear speck / chromatin remodeling / RNA helicase / chromosome / mRNA binding / nucleolus / positive regulation of DNA-templated transcription / protein-containing complex binding / enzyme binding Similarity search - Function
TatSF1-like, RNA recognition motif 1 / TatSF1-like / SF3B4, RNA recognition motif 2 / Splicing factor SF3a60 binding domain / Splicing factor SF3a60 binding domain / Splicing factor 3A subunit 1, ubiquitin domain / U2 small nuclear ribonucleoprotein B'', RNA recognition motif 2 / U2 small nuclear ribonucleoprotein B'', RNA recognition motif 1 / : / Replication stress response SDE2 C-terminal ...TatSF1-like, RNA recognition motif 1 / TatSF1-like / SF3B4, RNA recognition motif 2 / Splicing factor SF3a60 binding domain / Splicing factor SF3a60 binding domain / Splicing factor 3A subunit 1, ubiquitin domain / U2 small nuclear ribonucleoprotein B'', RNA recognition motif 2 / U2 small nuclear ribonucleoprotein B'', RNA recognition motif 1 / : / Replication stress response SDE2 C-terminal / Cactus-binding C-terminus of cactin protein / SF3A2 domain / : / Pre-mRNA-splicing factor SF3a complex subunit 2 (Prp11) / Splicing factor SF3a60 /Prp9 subunit, C-terminal / SF3A3 domain / SF3a60/Prp9 C-terminal / Pre-mRNA-splicing factor SF3A3, of SF3a complex, Prp9 / SF3B4, RNA recognition motif 1 / : / Splicing factor 3A subunit 1, conserved domain / Splicing factor 3A subunit 1 / Pre-mRNA splicing factor PRP21 like protein / : / : / Domain of unknown function DUF382 / Domain of unknown function (DUF382) / SWAP/Surp / SWAP/Surp superfamily / Surp module / SURP motif repeat profile. / Suppressor-of-White-APricot splicing regulator / Splicing factor 3B, subunit 5 / Splicing factor 3B subunit 1 / Splicing factor 3B subunit 1 / Zinc-finger of C2H2 type / PSP, proline-rich / PSP / proline-rich domain in spliceosome associated proteins / Matrin/U1-C, C2H2-type zinc finger / Zinc finger matrin-type profile. / PHF5-like / PHF5-like protein / Splicing factor 3B subunit 5/RDS3 complex subunit 10 / Splicing factor 3B subunit 10 (SF3b10) / Splicing factor 3B subunit 1-like / Small ribonucleoprotein associated, SmB/SmN / U2 small nuclear ribonucleoprotein A' / U2A'/phosphoprotein 32 family A, C-terminal / occurring C-terminal to leucine-rich repeats / Small nuclear ribonucleoprotein D1 / Leucine-rich repeat / : / PPP2R1A-like HEAT repeat / SAP motif profile. / SAP domain / Putative DNA-binding (bihelical) motif predicted to be involved in chromosomal organisation / SAP domain / Small nuclear ribonucleoprotein Sm D2 / Matrin/U1-C-like, C2H2-type zinc finger / U1-like zinc finger / Small nuclear ribonucleoprotein Sm D3 / Small nuclear ribonucleoprotein G / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein F / Sm-like protein Lsm7/SmG / Like-Sm (LSM) domain containing protein, LSm4/SmD1/SmD3 / Sm-like protein Lsm6/SmF / LSM domain / LSM domain, eukaryotic/archaea-type / snRNP Sm proteins / DEAD-box subfamily ATP-dependent helicases signature. / ATP-dependent RNA helicase DEAD-box, conserved site / RNA helicase, DEAD-box type, Q motif / : / Sm domain profile. / DEAD-box RNA helicase Q motif profile. / : / RSE1/DDB1/CPSF1 second beta-propeller / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / : / CPSF A subunit region / RSE1/DDB1/CPSF1 first beta-propeller / LSM domain superfamily / Leucine-rich repeat profile. / Zinc finger C2H2 superfamily / DEAD/DEAH box helicase domain / DEAD/DEAH box helicase / Zinc finger C2H2-type / Leucine-rich repeat / RNA recognition motif / RNA recognition motif / Eukaryotic RNA Recognition Motif (RRM) profile. / RNA recognition motif domain / RNA-binding domain superfamily / Leucine-rich repeat domain superfamily / Helicase conserved C-terminal domain / Armadillo-like helical / Ubiquitin family Similarity search - Domain/homology
17S U2 SnRNP complex component HTATSF1 / Splicing factor 3B subunit 1 / U2 small nuclear ribonucleoprotein B'' / U2 small nuclear ribonucleoprotein A' / Small nuclear ribonucleoprotein-associated proteins B and B' / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein F / Small nuclear ribonucleoprotein G / Small nuclear ribonucleoprotein Sm D1 / Small nuclear ribonucleoprotein Sm D2 ...17S U2 SnRNP complex component HTATSF1 / Splicing factor 3B subunit 1 / U2 small nuclear ribonucleoprotein B'' / U2 small nuclear ribonucleoprotein A' / Small nuclear ribonucleoprotein-associated proteins B and B' / 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 / Splicing factor 3A subunit 3 / Splicing factor 3B subunit 2 / Splicing factor 3B subunit 3 / Splicing factor 3B subunit 4 / Splicing factor 3A subunit 2 / Splicing factor 3A subunit 1 / PHD finger-like domain-containing protein 5A / ATP-dependent RNA helicase DDX42 / Splicing factor 3B subunit 5 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 2.7 Å
National Natural Science Foundation of China (NSFC)
China
Citation
Journal: Nat Commun / Year: 2023 Title: Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly. Authors: Fenghua Yang / Tong Bian / Xiechao Zhan / Zhe Chen / Zhihan Xing / Nicolas A Larsen / Xiaofeng Zhang / Yigong Shi / Abstract: Three RNA helicases - DDX42, DDX46 and DHX15 - are found to be associated with human U2 snRNP, but their roles and mechanisms in U2 snRNP and spliceosome assembly are insufficiently understood. Here ...Three RNA helicases - DDX42, DDX46 and DHX15 - are found to be associated with human U2 snRNP, but their roles and mechanisms in U2 snRNP and spliceosome assembly are insufficiently understood. Here we report the cryo-electron microscopy (cryo-EM) structures of the DDX42-SF3b complex and a putative assembly precursor of 17S U2 snRNP that contains DDX42 (DDX42-U2 complex). DDX42 is anchored on SF3B1 through N-terminal sequences, with its N-plug occupying the RNA path of SF3B1. The binding mode of DDX42 to SF3B1 is in striking analogy to that of DDX46. In the DDX42-U2 complex, the N-terminus of DDX42 remains anchored on SF3B1, but the helicase domain has been displaced by U2 snRNA and TAT-SF1. Through in vitro assays, we show DDX42 and DDX46 are mutually exclusive in terms of binding to SF3b. Cancer-driving mutations of SF3B1 target the residues in the RNA path that directly interact with DDX42 and DDX46. These findings reveal the distinct roles of DDX42 and DDX46 in assembly of 17S U2 snRNP and provide insights into the mechanisms of SF3B1 cancer mutations.
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