mRNA branch site recognition / positive regulation of RNA binding / mRNA splice site recognition / splicing factor binding / U4/U6 snRNP / 7-methylguanosine cap hypermethylation / pICln-Sm protein complex / ATP-dependent activity, acting on RNA / small nuclear ribonucleoprotein complex / SMN-Sm protein complex ...mRNA branch site recognition / positive regulation of RNA binding / mRNA splice site recognition / splicing factor binding / U4/U6 snRNP / 7-methylguanosine cap hypermethylation / pICln-Sm protein complex / ATP-dependent activity, acting on RNA / small nuclear ribonucleoprotein complex / SMN-Sm protein complex / spliceosomal tri-snRNP complex / mRNA cis splicing, via spliceosome / U2-type spliceosomal complex / commitment complex / U2-type prespliceosome assembly / poly(U) RNA binding / U4 snRNP / positive regulation of mRNA splicing, via spliceosome / U2 snRNP / U1 snRNP / pre-mRNA 5'-splice site binding / U2-type prespliceosome / precatalytic spliceosome / spliceosomal complex assembly / mRNA 5'-splice site recognition / regulation of RNA splicing / U5 snRNP / U2 snRNA binding / spliceosomal snRNP assembly / U1 snRNA binding / U4/U6 x U5 tri-snRNP complex / catalytic step 2 spliceosome / spliceosomal complex / mRNA splicing, via spliceosome / nucleic acid binding / RNA helicase activity / ヘリカーゼ / response to xenobiotic stimulus / mRNA binding / 核小体 / ATP hydrolysis activity / RNA binding / zinc ion binding / ATP binding / 細胞核 / 細胞質基質 / 細胞質 類似検索 - 分子機能
Luc7-related / LUC7 N_terminus / Snu56-like U1 small nuclear ribonucleoprotein component / Snu56-like U1 small nuclear ribonucleoprotein component / Pre-mRNA-splicing factor Prp9, N-terminal / Pre-mRNA-splicing factor PRP9 N-terminus / Pre-mRNA-processing factor Prp40 / U1 small nuclear ribonucleoprotein C / U1 small nuclear ribonucleoprotein of 70kDa N-terminal / U1 small nuclear ribonucleoprotein of 70kDa MW N terminal ...Luc7-related / LUC7 N_terminus / Snu56-like U1 small nuclear ribonucleoprotein component / Snu56-like U1 small nuclear ribonucleoprotein component / Pre-mRNA-splicing factor Prp9, N-terminal / Pre-mRNA-splicing factor PRP9 N-terminus / Pre-mRNA-processing factor Prp40 / U1 small nuclear ribonucleoprotein C / U1 small nuclear ribonucleoprotein of 70kDa N-terminal / U1 small nuclear ribonucleoprotein of 70kDa MW N terminal / U1-C, C2H2-type zinc finger / U1 zinc finger / FF domain / FF domain / FF domain superfamily / FF domain profile. / Contains two conserved F residues / RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) / SF3A2 domain / Pre-mRNA-splicing factor SF3a complex subunit 2 (Prp11) / PWI domain / Splicing factor SF3a60 /Prp9 subunit, C-terminal / SF3A3 domain / SF3B4, RNA recognition motif 1 / SF3a60/Prp9 C-terminal / Pre-mRNA-splicing factor SF3A3, of SF3a complex, Prp9 / PWI, domain in splicing factors / Splicing factor 3A subunit 1 / Splicing factor 3A subunit 1, conserved domain / Pre-mRNA splicing factor PRP21 like protein / Domain of unknown function DUF382 / Domain of unknown function (DUF382) / SWAP/Surp / SWAP/Surp superfamily / Surp module / Zinc-finger of C2H2 type / SURP motif repeat profile. / Suppressor-of-White-APricot splicing regulator / 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. / Zinc-finger double-stranded RNA-binding / Zinc finger, double-stranded RNA binding / U2A'/phosphoprotein 32 family A, C-terminal / occurring C-terminal to leucine-rich repeats / ロイシンリッチリピート / Small nuclear ribonucleoprotein Sm D3 / Small nuclear ribonucleoprotein Sm D2 / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein G / Small nuclear ribonucleoprotein F / Sm-like protein Lsm7/SmG / Like-Sm (LSM) domain containing protein, LSm4/SmD1/SmD3 / Matrin/U1-C-like, C2H2-type zinc finger / U1-like zinc finger / Sm-like protein Lsm6/SmF / LSM domain / LSM domain, eukaryotic/archaea-type / snRNP Sm proteins / HAT (Half-A-TPR) repeat / HAT (Half-A-TPR) repeats / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / Mono-functional DNA-alkylating methyl methanesulfonate N-term / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / CPSF A subunit region / : / Sm domain profile. / DEAD-box subfamily ATP-dependent helicases signature. / ATP-dependent RNA helicase DEAD-box, conserved site / RNA helicase, DEAD-box type, Q motif / DEAD-box RNA helicase Q motif profile. / LSM domain superfamily / WWドメイン / WW/rsp5/WWP domain signature. / WW domain superfamily / WW/rsp5/WWP domain profile. / Domain with 2 conserved Trp (W) residues / WWドメイン / ジンクフィンガー / Zinc finger C2H2 superfamily / Leucine-rich repeat profile. / DEAD/DEAH box helicase / DEAD/DEAH box helicase domain / Zinc finger C2H2-type / ロイシンリッチリピート / RNA認識モチーフ / RNA認識モチーフ / Eukaryotic RNA Recognition Motif (RRM) profile. / RNA recognition motif domain / Helicase conserved C-terminal domain / Leucine-rich repeat domain superfamily / RNA-binding domain superfamily / Armadillo-like helical 類似検索 - ドメイン・相同性
RDS3 complex subunit 10 / Pre-mRNA-splicing factor PRP9 / Pre-mRNA-processing ATP-dependent RNA helicase PRP5 / Pre-mRNA-splicing factor PRP21 / U1 small nuclear ribonucleoprotein A / Pre-mRNA-processing protein PRP40 / Pre-mRNA-processing factor 39 / Small nuclear ribonucleoprotein-associated protein B / Small nuclear ribonucleoprotein G / U2 small nuclear ribonucleoprotein B'' ...RDS3 complex subunit 10 / Pre-mRNA-splicing factor PRP9 / Pre-mRNA-processing ATP-dependent RNA helicase PRP5 / Pre-mRNA-splicing factor PRP21 / U1 small nuclear ribonucleoprotein A / Pre-mRNA-processing protein PRP40 / Pre-mRNA-processing factor 39 / Small nuclear ribonucleoprotein-associated protein B / Small nuclear ribonucleoprotein G / U2 small nuclear ribonucleoprotein B'' / Small nuclear ribonucleoprotein Sm D3 / U2 snRNP component HSH155 / U1 small nuclear ribonucleoprotein component SNU71 / Small nuclear ribonucleoprotein F / Protein NAM8 / U1 small nuclear ribonucleoprotein 70 kDa homolog / Small nuclear ribonucleoprotein Sm D1 / Cold sensitive U2 snRNA suppressor 1 / U1 small nuclear ribonucleoprotein component PRP42 / 56 kDa U1 small nuclear ribonucleoprotein component / Pre-mRNA-splicing factor RSE1 / U1 small nuclear ribonucleoprotein C / Small nuclear ribonucleoprotein Sm D2 / Pre-mRNA-splicing factor RDS3 / Pre-mRNA-splicing factor PRP11 / Protein LUC7 / U2 small nuclear ribonucleoprotein A' / Small nuclear ribonucleoprotein E / Protein HSH49 類似検索 - 構成要素
ジャーナル: Nature / 年: 2021 タイトル: Structural insights into how Prp5 proofreads the pre-mRNA branch site. 著者: Zhenwei Zhang / Norbert Rigo / Olexandr Dybkov / Jean-Baptiste Fourmann / Cindy L Will / Vinay Kumar / Henning Urlaub / Holger Stark / Reinhard Lührmann / 要旨: During the splicing of introns from precursor messenger RNAs (pre-mRNAs), the U2 small nuclear ribonucleoprotein (snRNP) must undergo stable integration into the spliceosomal A complex-a poorly ...During the splicing of introns from precursor messenger RNAs (pre-mRNAs), the U2 small nuclear ribonucleoprotein (snRNP) must undergo stable integration into the spliceosomal A complex-a poorly understood, multistep process that is facilitated by the DEAD-box helicase Prp5 (refs. ). During this process, the U2 small nuclear RNA (snRNA) forms an RNA duplex with the pre-mRNA branch site (the U2-BS helix), which is proofread by Prp5 at this stage through an unclear mechanism. Here, by deleting the branch-site adenosine (BS-A) or mutating the branch-site sequence of an actin pre-mRNA, we stall the assembly of spliceosomes in extracts from the yeast Saccharomyces cerevisiae directly before the A complex is formed. We then determine the three-dimensional structure of this newly identified assembly intermediate by cryo-electron microscopy. Our structure indicates that the U2-BS helix has formed in this pre-A complex, but is not yet clamped by the HEAT domain of the Hsh155 protein (Hsh155), which exhibits an open conformation. The structure further reveals a large-scale remodelling/repositioning of the U1 and U2 snRNPs during the formation of the A complex that is required to allow subsequent binding of the U4/U6.U5 tri-snRNP, but that this repositioning is blocked in the pre-A complex by the presence of Prp5. Our data suggest that binding of Hsh155 to the bulged BS-A of the U2-BS helix triggers closure of Hsh155, which in turn destabilizes Prp5 binding. Thus, Prp5 proofreads the branch site indirectly, hindering spliceosome assembly if branch-site mutations prevent the remodelling of Hsh155. Our data provide structural insights into how a spliceosomal helicase enhances the fidelity of pre-mRNA splicing.