CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3' processing.

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 Dev

journal_title

Genes & development

authors

Chan SL,Huppertz I,Yao C,Weng L,Moresco JJ,Yates JR 3rd,Ule J,Manley JL,Shi Y

doi

10.1101/gad.250993.114

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

2370-80

issue

21

eissn

0890-9369

issn

1549-5477

pii

gad.250993.114

journal_volume

28

pub_type

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