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Genes Dev. 2014 Nov 1;28(21):2370-80. doi: 10.1101/gad.250993.114. Epub 2014 Oct 9.

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

Author information

1
Department of Microbiology and Molecular Genetics, School of Medicine, University of California at Irvine, Irvine, California 92697, USA;
2
Department of Molecular Neuroscience, University College London Institute of Neurology, London WC1N 3BG, United Kingdom; Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom;
3
Department of Microbiology and Molecular Genetics, School of Medicine, University of California at Irvine, Irvine, California 92697, USA; Institute for Genomics and Bioinformatics, Department of Computer Science, University of California at Irvine Irvine, California 92697, USA;
4
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA;
5
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

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.

KEYWORDS:

cleavage and polyadenylation; mRNA 3′ processing; polyadenylation signal

PMID:
25301780
PMCID:
PMC4215182
DOI:
10.1101/gad.250993.114
[Indexed for MEDLINE]
Free PMC Article

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