The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei

Anna Kelner, Michele Tinti, Maria Guther, Bernardo J. Foth, Lia Chappell, Matthew Berriman, Victoria Cowling (Lead / Corresponding author), Michael Ferguson (Lead / Corresponding author)

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3 Citations (Scopus)
164 Downloads (Pure)

Abstract

Messenger RNA is modified by the addition of a 5′ methylated cap structure, which protects the transcript and recruits protein complexes that mediate RNA processing and/or the initiation of translation. Two genes encoding mRNA cap methyltransferases have been identified in T. brucei: TbCMT1 and TbCGM1. Here we analysed the impact of TbCMT1 gene deletion on bloodstream form T. brucei cells. TbCMT1 was dispensable for parasite proliferation in in vitro culture. However, significantly decreased parasitemia was observed in mice inoculated with TbCMT1 null and conditional null cell lines. Using RNA-Seq, we observed that several cysteine peptidase mRNAs were downregulated in TbCMT1 null cells lines. The cysteine peptidase Cathepsin-L was also shown to be reduced at the protein level in TbCMT1 null cell lines. Our data suggest that TbCMT1 is not essential to bloodstream form T. brucei growth in vitro or in vivo but that it contributes significantly to parasite virulence in vivo.
Original languageEnglish
Article numbere0201263
Pages (from-to)1-14
Number of pages14
JournalPLoS ONE
Volume13
Issue number7
DOIs
Publication statusPublished - 24 Jul 2018

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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