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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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

Fingerprint

bloodstream forms
Trypanosoma brucei
Null Lymphocytes
Trypanosoma brucei brucei
methyltransferases
Methyltransferases
Virulence Factors
virulence
Genes
peptidases
Cells
cell lines
Cell Line
Messenger RNA
Cysteine
cysteine
Parasites
Peptide Hydrolases
RNA
cathepsin L

Cite this

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title = "The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei",
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.",
author = "Anna Kelner and Michele Tinti and Maria Guther and Foth, {Bernardo J.} and Lia Chappell and Matthew Berriman and Victoria Cowling and Michael Ferguson",
note = "Funding: Wellcome Trust grant WT 802937",
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T1 - The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei

AU - Kelner, Anna

AU - Tinti, Michele

AU - Guther, Maria

AU - Foth, Bernardo J.

AU - Chappell, Lia

AU - Berriman, Matthew

AU - Cowling, Victoria

AU - Ferguson, Michael

N1 - Funding: Wellcome Trust grant WT 802937

PY - 2018/7/24

Y1 - 2018/7/24

N2 - 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.

AB - 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.

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