The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei.
Anna KelnerMichele TintiMaria Lucia S GutherBernardo J FothLia ChappellMatthew BerrimanVictoria Haigh CowlingMichael A J FergusonPublished in: PloS one (2018)
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.
Keyphrases
- rna seq
- induced apoptosis
- single cell
- genome wide
- escherichia coli
- cell cycle arrest
- staphylococcus aureus
- pseudomonas aeruginosa
- binding protein
- gram negative
- genome wide identification
- signaling pathway
- antimicrobial resistance
- protein protein
- biofilm formation
- adipose tissue
- genome wide analysis
- gene expression
- endoplasmic reticulum stress
- metabolic syndrome
- machine learning
- toxoplasma gondii
- fluorescent probe
- oxidative stress
- cell death
- dna methylation
- multidrug resistant
- life cycle