Evidence for a capping enzyme with specificity for the trypanosome spliced leader RNA

Mol Biochem Parasitol. 2007 Dec;156(2):246-54. doi: 10.1016/j.molbiopara.2007.09.001. Epub 2007 Sep 15.

Abstract

Capping of the pre-mRNA 5' end by addition a monomethylated guanosine cap (m(7)G) is an essential and the earliest modification in the biogenesis of mRNA. The reaction is catalyzed by three enzymes: triphosphatase, guanylyltransferase, and (guanine N-7) methyltransferase. Whereas this modification occurs co-transcriptionally in most eukaryotic organisms, trypanosomatid protozoa mRNAs acquire the m(7)G cap by trans-splicing, which entails the transfer of the capped spliced leader (SL) from the SL RNA to the mRNA. Intriguingly, the genomes of all trypanosomatid protozoa sequenced to date possess two distinct proteins with the signature motifs of guanylyltransferases: TbCGM1 and the previously characterized TbCE1. Here we provide biochemical evidence that TbCgm1 is a capping enzyme. Whereas RNAi-induced downregulation of TbCe1 had no phenotypic consequences, we found that TbCGM1 is essential for trypanosome viability and is required for SL RNA capping. Furthermore, consistent with co-transcriptional addition of the m(7)G cap, chromatin immunoprecipitation revealed recruitment of TbCgm1 to the SL RNA genes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Survival
  • Chromatin Immunoprecipitation
  • Gene Silencing
  • Genes, Essential
  • Nucleotidyltransferases / metabolism*
  • Protein Binding
  • Protozoan Proteins / metabolism*
  • RNA Caps / metabolism*
  • RNA Interference
  • RNA, Spliced Leader / metabolism*
  • Substrate Specificity
  • Trypanosoma brucei brucei / enzymology*
  • Trypanosoma brucei brucei / genetics

Substances

  • Protozoan Proteins
  • RNA Caps
  • RNA, Spliced Leader
  • CGM1 protein, Trypanosoma brucei
  • Nucleotidyltransferases