mRNA splice site recognition / splicing factor binding / U4/U6 snRNP / 7-methylguanosine cap hypermethylation / pICln-Sm protein complex / positive regulation of mRNA splicing, via spliceosome / snRNP binding / small nuclear ribonucleoprotein complex / SMN-Sm protein complex / spliceosomal tri-snRNP complex ...mRNA splice site recognition / splicing factor binding / U4/U6 snRNP / 7-methylguanosine cap hypermethylation / pICln-Sm protein complex / positive regulation of mRNA splicing, via spliceosome / snRNP binding / small nuclear ribonucleoprotein complex / SMN-Sm protein complex / spliceosomal tri-snRNP complex / U2-type spliceosomal complex / commitment complex / mRNA cis splicing, via spliceosome / U2-type prespliceosome assembly / U4 snRNP / U2 snRNP / U1 snRNP / poly(U) RNA binding / U2-type prespliceosome / pre-mRNA 5'-splice site binding / precatalytic spliceosome / spliceosomal complex assembly / mRNA 5'-splice site recognition / Prp19 complex / 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 / response to xenobiotic stimulus / mRNA binding / RNA binding / zinc ion binding / nucleus / cytosol / cytoplasm 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 / SNU71 RNA binding domain / SNU71 N-terminal / Pre-mRNA-splicing factor Prp9, N-terminal / Pre-mRNA-splicing factor PRP9 N-terminus / U1 small nuclear ribonucleoprotein C / PRP39 C-terminal HAT repeat ...Luc7-related / LUC7 N_terminus / Snu56-like U1 small nuclear ribonucleoprotein component / Snu56-like U1 small nuclear ribonucleoprotein component / SNU71 RNA binding domain / SNU71 N-terminal / Pre-mRNA-splicing factor Prp9, N-terminal / Pre-mRNA-splicing factor PRP9 N-terminus / U1 small nuclear ribonucleoprotein C / PRP39 C-terminal HAT repeat / 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 / RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) / PWI domain / PWI, domain in splicing factors / SF3A2 domain / : / Pre-mRNA-splicing factor SF3a complex subunit 2 (Prp11) / PRP39 N-terminal HAT repeat / 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 / : / 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. / Zinc-finger double-stranded RNA-binding / Zinc finger, double-stranded RNA binding / U2 small nuclear ribonucleoprotein A' / U2A'/phosphoprotein 32 family A, C-terminal / occurring C-terminal to leucine-rich repeats / : / PPP2R1A-like HEAT repeat / Leucine-rich repeat / 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 / LSM domain / LSM domain, eukaryotic/archaea-type / snRNP Sm proteins / HAT (Half-A-TPR) repeat / HAT (Half-A-TPR) repeats / 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 / : / Sm domain profile. / LSM domain superfamily / zinc finger / Leucine-rich repeat profile. / Zinc finger C2H2 superfamily / 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 / Armadillo-like helical / Tetratricopeptide-like helical domain superfamily / Armadillo-type fold / Nucleotide-binding alpha-beta plait domain superfamily 類似検索 - ドメイン・相同性
RDS3 complex subunit 10 / Pre-mRNA-splicing factor PRP9 / Pre-mRNA-splicing factor PRP21 / U1 small nuclear ribonucleoprotein A / 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 ...RDS3 complex subunit 10 / Pre-mRNA-splicing factor PRP9 / Pre-mRNA-splicing factor PRP21 / U1 small nuclear ribonucleoprotein A / 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: 2018 タイトル: Prespliceosome structure provides insights into spliceosome assembly and regulation. 著者: Clemens Plaschka / Pei-Chun Lin / Clément Charenton / Kiyoshi Nagai / 要旨: The spliceosome catalyses the excision of introns from pre-mRNA in two steps, branching and exon ligation, and is assembled from five small nuclear ribonucleoprotein particles (snRNPs; U1, U2, U4, ...The spliceosome catalyses the excision of introns from pre-mRNA in two steps, branching and exon ligation, and is assembled from five small nuclear ribonucleoprotein particles (snRNPs; U1, U2, U4, U5, U6) and numerous non-snRNP factors. For branching, the intron 5' splice site and the branch point sequence are selected and brought by the U1 and U2 snRNPs into the prespliceosome, which is a focal point for regulation by alternative splicing factors. The U4/U6.U5 tri-snRNP subsequently joins the prespliceosome to form the complete pre-catalytic spliceosome. Recent studies have revealed the structural basis of the branching and exon-ligation reactions, however, the structural basis of the early events in spliceosome assembly remains poorly understood. Here we report the cryo-electron microscopy structure of the yeast Saccharomyces cerevisiae prespliceosome at near-atomic resolution. The structure reveals an induced stabilization of the 5' splice site in the U1 snRNP, and provides structural insights into the functions of the human alternative splicing factors LUC7-like (yeast Luc7) and TIA-1 (yeast Nam8), both of which have been linked to human disease. In the prespliceosome, the U1 snRNP associates with the U2 snRNP through a stable contact with the U2 3' domain and a transient yeast-specific contact with the U2 SF3b-containing 5' region, leaving its tri-snRNP-binding interface fully exposed. The results suggest mechanisms for 5' splice site transfer to the U6 ACAGAGA region within the assembled spliceosome and for its subsequent conversion to the activation-competent B-complex spliceosome. Taken together, the data provide a working model to investigate the early steps of spliceosome assembly.
タンパク質・ペプチド: U1 small nuclear ribonucleoprotein A,U1 small nuclear ribonucleoprotein A,U1 small nuclear ribonucleoprotein A,U1 small nuclear ribonucleoprotein A,U1 small nuclear ribonucleoprotein A
タンパク質・ペプチド: U1 small nuclear ribonucleoprotein 70 kDa homolog,U1 small nuclear ribonucleoprotein 70 kDa homolog,U1 small nuclear ribonucleoprotein 70 kDa homolog
タンパク質・ペプチド: U1 small nuclear ribonucleoprotein C
タンパク質・ペプチド: Pre-mRNA-processing factor 39
タンパク質・ペプチド: U1 small nuclear ribonucleoprotein component PRP42
タンパク質・ペプチド: Protein NAM8
タンパク質・ペプチド: 56 kDa U1 small nuclear ribonucleoprotein component
タンパク質・ペプチド: Protein LUC7,Protein LUC7,Protein LUC7
RNA: Yeast UBC4 pre-mRNA (mutant)
タンパク質・ペプチド: U1 small nuclear ribonucleoprotein component SNU71
凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: FEI VITROBOT MARK III 詳細: Grids were blotted for 2-3.5 s and vitrified by plunging into liquid ethane with a FEI Vitrobot Mark III operated at 4 degree Celsius and 100% humidity..