STRUCTURAL BASIS FOR SEQUENCE-NONSPECIFIC RECOGNITION OF 5'-CAPPED MESSENGER-RNA BY A CAP-MODIFYING ENZYME

Sequence-nonspecific binding of RNA, recognition of a 7-methylguanosin e 5' mRNA cap, and methylation of a nucleic acid backbone are three cr ucial and ubiquitous events in eukaryotic nucleic acid processing and function. These three events occur concurrently in the modification of vaccinia transcripts by the methyltransferase VP39. We report the cry stal structure of a ternary complex comprising VP39, coenzyme product S-adenosylhomocysteine, and a 5' m(7)G-capped, single-stranded RNA hex amer. This structure reveals a novel and general mechanism for sequenc e-nonspecific recognition of the mRNA transcript in which the protein interacts solely with the sugar-phosphate backbone of a short, single- stranded RNA helix. This report represents the first direct and detail ed view of a protein complexed with single-stranded RNA or 5'-capped m RNA.