Structure of the Rna15 RRM-RNA complex reveals the molecular basis of GU specificity in transcriptional 3'-end processing factors.
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.
Pancevac
Christina
C
Division of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Goldstone
David C
DC
Ramos
Andres
A
Taylor
Ian A
IA
D020816:Amino Acid Motifs; D001665:Binding Sites; D006147:Guanine; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D026721:RNA 3' End Processing; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D014498:Uracil; D039221:mRNA Cleavage and Polyadenylation Factors / Q000737:chemistry* / Q000378:metabolism
D029701:Saccharomyces cerevisiae Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; C512635:RNA15 protein, S cerevisiae; D014498:Uracil; D006147:Guanine; D012313:RNA