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
Celljournal_title
Cellauthors
Zhang X,Yan C,Hang J,Finci LI,Lei J,Shi Ydoi
10.1016/j.cell.2017.04.033subject
Has Abstractpub_date
2017-05-18 00:00:00pages
918-929.e14issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(17)30487-7journal_volume
169pub_type
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