Author:
Chan Serena L.,Huppertz Ina,Yao Chengguo,Weng Lingjie,Moresco James J.,Yates John R.,Ule Jernej,Manley James L.,Shi Yongsheng
Abstract
AAUAAA is the most highly conserved motif in eukaryotic mRNA polyadenylation sites and, in mammals, is specifically recognized by the multisubunit CPSF (cleavage and polyadenylation specificity factor) complex. Despite its critical functions in mRNA 3′ end formation, the molecular basis for CPSF–AAUAAA interaction remains poorly defined. The CPSF subunit CPSF160 has been implicated in AAUAAA recognition, but direct evidence has been lacking. Using in vitro and in vivo assays, we unexpectedly found that CPSF subunits CPSF30 and Wdr33 directly contact AAUAAA. Importantly, the CPSF30–RNA interaction is essential for mRNA 3′ processing and is primarily mediated by its zinc fingers 2 and 3, which are specifically targeted by the influenza protein NS1A to suppress host mRNA 3′ processing. Our data suggest that AAUAAA recognition in mammalian mRNA 3′ processing is more complex than previously thought and involves multiple protein–RNA interactions.
Funder
National Institutes of Health
American Cancer Society
Marie Curie Initial Training Network RNPnet
National Center for Research Resources
National Institute of General Medical Sciences
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
198 articles.
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