Processing the message: structural insights into capping and decapping mRNA

The 5′ m7GpppN cap plays an essential role in the life cycle of eukaryotic mRNA and is required for efficient pre-mRNA splicing, export, stability and translation. Nascent pre-mRNA is capped through a series of three enzymatic steps that result in a 5′ N7-methyl guanosine linked by an inverted 5′-5′ triphosphate bridge to the first nucleotide of the transcript. Early structural studies revealed the mechanisms employed in the first two steps of capping, and more recent structural studies have completed the suite of capping activities and shed light on the mechanisms that target the capping apparatus to the phosphorylated C-terminal domain of RNA polymerase II. RNA decay pathways also target the RNA cap structure. After deadenylation of polyadenylated mRNA, enzymes of the 5′-3′ decay pathway hydrolyze the mRNA cap to expose the 5′ RNA end to 5′-3′ exoribonuclease activities. In the 3′-5′ decay pathway, exosome-mediated degradation of RNA occurs from the 3′ end after deadenylation, ultimately generating a cap structure that is hydrolyzed by enzymes of this pathway. Recent structural studies have illuminated the mechanisms employed for decapping mRNA in both 5′-3′ and 3′-5′ decay pathways.