The mRNA Capping Apparatus as Drug Target and Guide to Eukaryotic Phylogeny

The 5′ cap is a distinctive feature of eukaryotic cellularand viral messenger RNA. The cap structure consists of7-methyl guanosine linked via an inverted 5′–5′ triphosphate bridge to the initiating nucleoside of the transcript(Fig. 1). The cap is formed by enzymatic modification ofnascent pre-mRNAs as they are being synthesized by cellular or viral RNA polymerases. Capping of cellularRNAs in vivo is effectively restricted to the transcriptsmade by nuclear RNA polymerase II (i.e., pre-mRNAsand certain small nuclear RNAs). Recent studies haveshown that the targeting of cap formation is achievedthrough direct binding of the cellular capping apparatusto the RNA polymerase II elongation complex (Shuman1997). Many eukaryotic DNA and RNA viruses, especially those that replicate in the cytoplasm, encode theirown RNA polymerase and their own capping apparatus.In such systems, the viral capping enzymes interact with,or are subunits of, the viral transcription complex (Haglerand Shuman 1992; Guarino et al. 1998)...