Viral and cellular mRNA capping: past and prospects

Abstract

This chapter focuses on the history of the discovery of cap and an update of research on viral and cellular-messenger RNA (mRNA) capping. Cap structures of the type m⁷ GpppN(m)pN(m)p are present at the 5′ ends of nearly all eukaryotic cellular and viral mRNAs. A cap is added to cellular mRNA precursors and to the transcripts of viruses that replicate in the nucleus during the initial phases of transcription and before other processing events, including internal N⁶A methylation, 3′-poly (A) addition, and exon splicing. Despite the variations on the methylation theme, the important biological consequences of a cap structure appear to correlate with the N⁷-methyl on the 5′-terminal G and the two pyrophosphoryl bonds that connect m⁷G in a 5′–5′ configuration to the first nucleotide of mRNA. In addition to elucidating the biochemical mechanisms of capping and the downstream effects of this 5′- modification on gene expression, the advent of gene cloning has made available an ever-increasing amount of information on the proteins responsible for producing caps and the functional effects of other cap-related interactions. Genetic approaches have demonstrated the lethal consequences of cap failure in yeasts, and complementation studies have shown the evolutionary functional conservation of capping from unicellular to metazoan organisms.