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TitleAn Atomic Structure of the Human Spliceosome.
Journal, issue, pagesCell, Vol. 169, Issue 5, Page 918-929.e14, Year 2017
Publish dateMay 18, 2017
AuthorsXiaofeng Zhang / Chuangye Yan / Jing Hang / Lorenzo I Finci / Jianlin Lei / Yigong Shi /
PubMed AbstractMechanistic understanding of pre-mRNA splicing requires detailed structural information on various states of the spliceosome. Here we report the cryo electron microscopy (cryo-EM) structure of the ...Mechanistic understanding of pre-mRNA splicing requires detailed structural information on various states of the spliceosome. Here we report the cryo electron microscopy (cryo-EM) structure of the human spliceosome just before exon ligation (the C complex) at an average resolution of 3.76 Å. The splicing factor Prp17 stabilizes the active site conformation. The step II factor Slu7 adopts an extended conformation, binds Prp8 and Cwc22, and is poised for selection of the 3'-splice site. Remarkably, the intron lariat traverses through a positively charged central channel of RBM22; this unusual organization suggests mechanisms of intron recruitment, confinement, and release. The protein PRKRIP1 forms a 100-Å α helix linking the distant U2 snRNP to the catalytic center. A 35-residue fragment of the ATPase/helicase Prp22 latches onto Prp8, and the quaternary exon junction complex (EJC) recognizes upstream 5'-exon sequences and associates with Cwc22 and the GTPase Snu114. These structural features reveal important mechanistic insights into exon ligation.
External linksCell / PubMed:28502770
MethodsEM (single particle)
Resolution3.6 Å
Structure data

6721

5xjc

EMDB-6721, PDB-5xjc:
Cryo-EM structure of the human spliceosome just prior to exon ligation at 3.6 angstrom
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE / Phytic acid

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM / Guanosine triphosphate

ChemComp-MG:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

ChemComp-ZN:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

Source
  • homo sapiens (human)
  • Human (human)
  • human adenovirus 2
KeywordsSPLICING / RNA splicing / human spliceosome / C* complex / atomic structure / step 2 factors / EJC

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