Journal
GENES & DEVELOPMENT
Volume 28, Issue 21, Pages 2370-2380Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.250993.114
Keywords
mRNA 3 ' processing; cleavage and polyadenylation; polyadenylation signal
Categories
Funding
- National Institutes of Health (NIH) [GM090056]
- American Cancer Society [RSG-12-186]
- University of California at Irvine
- Marie Curie Initial Training Network RNPnet [289007]
- National Center for Research Resources [5P41RR011823]
- National Institute of General Medical Sciences [8 P41 GM103533]
- NIH [GM28983]
- MRC [MC_U105185858] Funding Source: UKRI
- Medical Research Council [MC_U105185858] Funding Source: researchfish
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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.
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