Journal
NUCLEIC ACIDS RESEARCH
Volume 38, Issue 9, Pages 3119-3132Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq002
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Funding
- MRC, UK
- Medical Research Council [MC_U117574558, MC_U117565647, MC_U117533887] Funding Source: researchfish
- MRC [MC_U117533887, MC_U117565647, MC_U117574558] Funding Source: UKRI
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Rna15 is a core subunit of cleavage factor IA (CFIA), an essential transcriptional 3'-end processing factor from Saccharomyces cerevisiae. CFIA is required for polyA site selection/cleavage targeting RNA sequences that surround polyadenylation sites in the 3'-UTR of RNA polymerase-II transcripts. RNA recognition by CFIA is mediated by an RNA recognition motif (RRM) contained in the Rna15 subunit of the complex. We show here that Rna15 has a strong and unexpected preference for GU containing RNAs and reveal the molecular basis for a base selectivity mechanism that accommodates G or U but discriminates against C and A bases. This mode of base selectivity is rather different to that observed in other RRM-RNA structures and is structurally conserved in CstF64, the mammalian counterpart of Rna15. Our observations provide evidence for a highly conserved mechanism of base recognition amongst the 3'-end processing complexes that interact with the U-rich or U/G-rich elements at 3'-end cleavage/polyadenylation sites.
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