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

Serena L. Chan, Ina Huppertz, Chengguo Yao, Lingjie Weng, James J. Moresco, John R. Yates, Jernej Ule, James L. Manley, Yongsheng Shi

Research output: Contribution to journalArticle

89 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2370-2380
Number of pages11
JournalGenes and Development
Volume28
Issue number21
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

Keywords

  • Cleavage and polyadenylation
  • MRNA 3′ processing
  • Polyadenylation signal

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Chan, S. L., Huppertz, I., Yao, C., Weng, L., Moresco, J. J., Yates, J. R., Ule, J., Manley, J. L., & Shi, Y. (2014). CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3′ processing. Genes and Development, 28(21), 2370-2380. https://doi.org/10.1101/gad.250993.114