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.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Chan SL,Huppertz I,Yao C,Weng L,Moresco JJ,Yates JR 3rd,Ule J,Manley JL,Shi Ydoi
10.1101/gad.250993.114subject
Has Abstractpub_date
2014-11-01 00:00:00pages
2370-80issue
21eissn
0890-9369issn
1549-5477pii
gad.250993.114journal_volume
28pub_type
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