+検索条件
-Structure paper
タイトル | A human postcatalytic spliceosome structure reveals essential roles of metazoan factors for exon ligation. |
---|---|
ジャーナル・号・ページ | Science, Vol. 363, Issue 6428, Page 710-714, Year 2019 |
掲載日 | 2019年2月15日 |
著者 | Sebastian M Fica / Chris Oubridge / Max E Wilkinson / Andrew J Newman / Kiyoshi Nagai / |
PubMed 要旨 | During exon ligation, the spliceosome recognizes the 3'-splice site (3'SS) of precursor messenger RNA (pre-mRNA) through non-Watson-Crick pairing with the 5'SS and the branch adenosine, in a ...During exon ligation, the spliceosome recognizes the 3'-splice site (3'SS) of precursor messenger RNA (pre-mRNA) through non-Watson-Crick pairing with the 5'SS and the branch adenosine, in a conformation stabilized by Prp18 and Prp8. Here we present the 3.3-angstrom cryo-electron microscopy structure of a human postcatalytic spliceosome just after exon ligation. The 3'SS docks at the active site through conserved RNA interactions in the absence of Prp18. Unexpectedly, the metazoan-specific FAM32A directly bridges the 5'-exon and intron 3'SS of pre-mRNA and promotes exon ligation, as shown by functional assays. CACTIN, SDE2, and NKAP-factors implicated in alternative splicing-further stabilize the catalytic conformation of the spliceosome during exon ligation. Together these four proteins act as exon ligation factors. Our study reveals how the human spliceosome has co-opted additional proteins to modulate a conserved RNA-based mechanism for 3'SS selection and to potentially fine-tune alternative splicing at the exon ligation stage. |
リンク | Science / PubMed:30705154 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 5.9 Å |
構造データ | EMDB-4525: Human post-catalytic spliceosome (P complex) stalled with DHX8 K594A mutant, overall map EMDB-4526: EMDB-4527: EMDB-4528: EMDB-4529: EMDB-4530: EMDB-4532: EMDB-4533: EMDB-4534: EMDB-4535: |
化合物 | ChemComp-MG: ChemComp-K: ChemComp-ATP: ChemComp-GTP: ChemComp-ZN: ChemComp-IHP: |
由来 |
|
キーワード | SPLICING / spliceosome / RNA / complex |