An Atomic Structure of the Human Spliceosome.

Abstract:

: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.

journal_name

Cell

journal_title

Cell

authors

Zhang X,Yan C,Hang J,Finci LI,Lei J,Shi Y

doi

10.1016/j.cell.2017.04.033

subject

Has Abstract

pub_date

2017-05-18 00:00:00

pages

918-929.e14

issue

5

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(17)30487-7

journal_volume

169

pub_type

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