Grabbing the message: structural basis of mRNA 3'UTR recognition by Hrp1.
The recognition of specific signals encoded within the 3'-untranslated region of the newly transcribed mRNA triggers the assembly of a multiprotein machine that modifies its 3'-end. Hrp1 recognises one of such signals, the so-called polyadenylation enhancement element (PEE), promoting the recruitment of other polyadenylation factors in yeast. The molecular bases of this interaction are revealed here by the solution structure of a complex between Hrp1 and an oligonucleotide mimicking the PEE. Six consecutive bases (AUAUAU) are specifically recognised by two RNA-binding domains arranged in tandem. Both protein and RNA undergo significant conformational changes upon complex formation with a concomitant large surface burial of RNA bases. Key aspects of RNA specificity can be explained by the presence of intermolecular aromatic-aromatic contacts and hydrogen bonds. Altogether, the Hrp1-PEE structure represents one of the first steps towards understanding of the assembly of the cleavage and polyadenylation machinery at the atomic level.
Pérez-Cañadillas
José Manuel
JM
Laboratory of Molecular Biology, Medical Research Council, Cambridge, UK. jmperez@iqfr.csic.es
D020413:3' Untranslated Regions; D000225:Adenine / Q000737:chemistry; D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D026723:Polyadenylation; D011485:Protein Binding; D012333:RNA, Messenger / Q000737:chemistry*; D012266:Ribose / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics; D014498:Uracil / Q000737:chemistry; D039221:mRNA Cleavage and Polyadenylation Factors / Q000737:chemistry* / Q000235:genetics
D020413:3' Untranslated Regions; C512636:HRP1 protein, S cerevisiae; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D014498:Uracil; D012266:Ribose; D000225:Adenine