- EMDB-32074: The cryo-EM structure of the human pre-A complex -
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基本情報
登録情報
データベース: EMDB / ID: EMD-32074
タイトル
The cryo-EM structure of the human pre-A complex
マップデータ
The cryo-EM map for the U2 part of human pre-A complex
試料
複合体: human pre-A complex
複合体: human pre-A
タンパク質・ペプチド: x 24種
RNA: x 4種
複合体: pre-mRNA, 5SS
リガンド: x 2種
キーワード
human spliceosome / pre-A complex / PRP5 / A complex / U1 snRNP / U2 snRNP / SPLICING
機能・相同性
機能・相同性情報
nuclear body organization / negative regulation of protein refolding / U2AF complex / regulation of steroid biosynthetic process / U11/U12 snRNP / regulation of ATP-dependent activity / U2 snRNP binding / U7 snRNA binding / histone pre-mRNA DCP binding / U7 snRNP ...nuclear body organization / negative regulation of protein refolding / U2AF complex / regulation of steroid biosynthetic process / U11/U12 snRNP / regulation of ATP-dependent activity / U2 snRNP binding / U7 snRNA binding / histone pre-mRNA DCP binding / U7 snRNP / Leydig cell differentiation / histone pre-mRNA 3'end processing complex / SLBP independent Processing of Histone Pre-mRNAs / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / B-WICH complex / splicing factor binding / male sex determination / protein methylation / U12-type spliceosomal complex / 7-methylguanosine cap hypermethylation / U1 snRNP binding / RNA splicing, via transesterification reactions / methylosome / pICln-Sm protein complex / regulation of mRNA splicing, via spliceosome / positive regulation of mRNA splicing, via spliceosome / snRNP binding / small nuclear ribonucleoprotein complex / telomerase holoenzyme complex / SMN-Sm protein complex / P granule / telomerase RNA binding / spliceosomal tri-snRNP complex / U2-type precatalytic spliceosome / U2-type spliceosomal complex / commitment complex / mRNA cis splicing, via spliceosome / U2-type prespliceosome assembly / negative regulation of chaperone-mediated autophagy / U2-type catalytic step 2 spliceosome / SAGA complex / U4 snRNP / U2 snRNP / RNA Polymerase II Transcription Termination / U1 snRNP / U2-type prespliceosome / positive regulation of transcription by RNA polymerase III / pre-mRNA 5'-splice site binding / precatalytic spliceosome / positive regulation of transcription by RNA polymerase I / spliceosomal complex assembly / regulation of RNA splicing / mRNA 5'-splice site recognition / mRNA Splicing - Minor Pathway / mRNA 3'-splice site recognition / U5 snRNP / U2 snRNA binding / spliceosomal snRNP assembly / regulation of DNA repair / Cajal body / intercellular bridge / U1 snRNA binding / U4/U6 x U5 tri-snRNP complex / catalytic step 2 spliceosome / Hsp70 protein binding / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / mRNA Splicing - Major Pathway / RNA splicing / stem cell differentiation / spliceosomal complex / negative regulation of smooth muscle cell proliferation / negative regulation of protein catabolic process / mRNA splicing, via spliceosome / positive regulation of neuron projection development / B-WICH complex positively regulates rRNA expression / cytoplasmic ribonucleoprotein granule / nuclear matrix / fibrillar center / mRNA processing / transcription corepressor activity / snRNP Assembly / SARS-CoV-2 modulates host translation machinery / spermatogenesis / single-stranded RNA binding / RNA helicase activity / nuclear speck / nuclear body / RNA helicase / ribosome / chromatin remodeling / mRNA binding / protein-containing complex binding / positive regulation of DNA-templated transcription / nucleolus / enzyme binding / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / ATP hydrolysis activity / DNA binding / RNA binding 類似検索 - 分子機能
DnaJ homolog subfamily C member 8 / Splicing factor 1, helix-hairpin domain / : / Splicing factor 1 helix-hairpin domain / snRNP70, RNA recognition motif / : / KH-domain / U1 small nuclear ribonucleoprotein C / : / KHDC4/BBP-like, KH-domain type I ...DnaJ homolog subfamily C member 8 / Splicing factor 1, helix-hairpin domain / : / Splicing factor 1 helix-hairpin domain / snRNP70, RNA recognition motif / : / KH-domain / U1 small nuclear ribonucleoprotein C / : / KHDC4/BBP-like, KH-domain type I / U1 small nuclear ribonucleoprotein of 70kDa N-terminal / U1 small nuclear ribonucleoprotein of 70kDa MW N terminal / KH domain-containing BBP-like / : / U1-C, C2H2-type zinc finger / U1 zinc finger / SF3B4, RNA recognition motif 2 / Splicing factor SF3a60 binding domain / Splicing factor SF3a60 binding domain / Cactus-binding C-terminus of cactin protein / Splicing factor 3A subunit 1, ubiquitin domain / : / Replication stress response SDE2 C-terminal / SF3A2 domain / : / Pre-mRNA-splicing factor SF3a complex subunit 2 (Prp11) / U2 small nuclear ribonucleoprotein B'', RNA recognition motif 2 / U2 small nuclear ribonucleoprotein B'', RNA recognition motif 1 / Splicing factor SF3a60 /Prp9 subunit, C-terminal / SF3A3 domain / U1 small nuclear ribonucleoprotein A, RNA recognition motif 2 / SF3a60/Prp9 C-terminal / Pre-mRNA-splicing factor SF3A3, of SF3a complex, Prp9 / SF3B4, RNA recognition motif 1 / : / U1 small nuclear ribonucleoprotein A, RNA recognition motif 1 / Splicing factor 3B, subunit 5 / Splicing factor 3A subunit 1, conserved domain / Splicing factor 3A subunit 1 / Pre-mRNA splicing factor PRP21 like protein / Splicing factor 3B subunit 1 / : / Splicing factor 3B subunit 1 / : / 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 / Zinc-finger of C2H2 type / PHF5-like / PHF5-like protein / PSP, proline-rich / PSP / proline-rich domain in spliceosome associated proteins / Splicing factor 3B subunit 5/RDS3 complex subunit 10 / Splicing factor 3B subunit 10 (SF3b10) / Splicing factor 3B subunit 1-like / Matrin/U1-C, C2H2-type zinc finger / Zinc finger matrin-type profile. / Small ribonucleoprotein associated, SmB/SmN / U2 small nuclear ribonucleoprotein A' / Small nuclear ribonucleoprotein D1 / U2A'/phosphoprotein 32 family A, C-terminal / occurring C-terminal to leucine-rich repeats / : / PPP2R1A-like HEAT repeat / DnaJ domain / SAP motif profile. / SAP domain / Leucine-rich repeat / Putative DNA-binding (bihelical) motif predicted to be involved in chromosomal organisation / SAP domain / Small nuclear ribonucleoprotein Sm D3 / Small nuclear ribonucleoprotein Sm D2 / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein G / Small nuclear ribonucleoprotein F / Matrin/U1-C-like, C2H2-type zinc finger / U1-like zinc finger / Sm-like protein Lsm7/SmG / Like-Sm (LSM) domain containing protein, LSm4/SmD1/SmD3 / Sm-like protein Lsm6/SmF / DnaJ molecular chaperone homology domain / dnaJ domain profile. / LSM domain / LSM domain, eukaryotic/archaea-type / snRNP Sm proteins / Type-1 KH domain profile. / Chaperone J-domain superfamily / DnaJ domain / DEAD-box subfamily ATP-dependent helicases signature. / RSE1/DDB1/CPSF1 second beta-propeller / ATP-dependent RNA helicase DEAD-box, conserved site / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / : / CPSF A subunit region 類似検索 - ドメイン・相同性
Splicing factor 3B subunit 1 / DnaJ homolog subfamily C member 8 / U2 small nuclear ribonucleoprotein B'' / U1 small nuclear ribonucleoprotein 70 kDa / U1 small nuclear ribonucleoprotein A / U1 small nuclear ribonucleoprotein C / U2 small nuclear ribonucleoprotein A' / Small nuclear ribonucleoprotein-associated proteins B and B' / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein F ...Splicing factor 3B subunit 1 / DnaJ homolog subfamily C member 8 / U2 small nuclear ribonucleoprotein B'' / U1 small nuclear ribonucleoprotein 70 kDa / U1 small nuclear ribonucleoprotein A / U1 small nuclear ribonucleoprotein C / 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 / Splicing factor 1 / Probable ATP-dependent RNA helicase DDX46 / PHD finger-like domain-containing protein 5A / Splicing factor 3B subunit 5 類似検索 - 構成要素
生物種
Homo sapiens (ヒト) / unidentified adenovirus (ウイルス)
National Natural Science Foundation of China (NSFC)
中国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2024 タイトル: Structural insights into branch site proofreading by human spliceosome. 著者: Xiaofeng Zhang / Xiechao Zhan / Tong Bian / Fenghua Yang / Pan Li / Yichen Lu / Zhihan Xing / Rongyan Fan / Qiangfeng Cliff Zhang / Yigong Shi / 要旨: Selection of the pre-mRNA branch site (BS) by the U2 small nuclear ribonucleoprotein (snRNP) is crucial to prespliceosome (A complex) assembly. The RNA helicase PRP5 proofreads BS selection but the ...Selection of the pre-mRNA branch site (BS) by the U2 small nuclear ribonucleoprotein (snRNP) is crucial to prespliceosome (A complex) assembly. The RNA helicase PRP5 proofreads BS selection but the underlying mechanism remains unclear. Here we report the atomic structures of two sequential complexes leading to prespliceosome assembly: human 17S U2 snRNP and a cross-exon pre-A complex. PRP5 is anchored on 17S U2 snRNP mainly through occupation of the RNA path of SF3B1 by an acidic loop of PRP5; the helicase domain of PRP5 associates with U2 snRNA; the BS-interacting stem-loop (BSL) of U2 snRNA is shielded by TAT-SF1, unable to engage the BS. In the pre-A complex, an initial U2-BS duplex is formed; the translocated helicase domain of PRP5 stays with U2 snRNA and the acidic loop still occupies the RNA path. The pre-A conformation is specifically stabilized by the splicing factors SF1, DNAJC8 and SF3A2. Cancer-derived mutations in SF3B1 damage its association with PRP5, compromising BS proofreading. Together, these findings reveal key insights into prespliceosome assembly and BS selection or proofreading by PRP5.