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

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 TbCG...

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Autores principales: Kelner, Anna, Tinti, Michele, Guther, Maria Lucia S., Foth, Bernardo J., Chappell, Lia, Berriman, Matthew, Cowling, Victoria Haigh, Ferguson, Michael A. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057678/
https://www.ncbi.nlm.nih.gov/pubmed/30040830
http://dx.doi.org/10.1371/journal.pone.0201263
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author Kelner, Anna
Tinti, Michele
Guther, Maria Lucia S.
Foth, Bernardo J.
Chappell, Lia
Berriman, Matthew
Cowling, Victoria Haigh
Ferguson, Michael A. J.
author_facet Kelner, Anna
Tinti, Michele
Guther, Maria Lucia S.
Foth, Bernardo J.
Chappell, Lia
Berriman, Matthew
Cowling, Victoria Haigh
Ferguson, Michael A. J.
author_sort Kelner, Anna
collection PubMed
description 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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spelling pubmed-60576782018-08-06 The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei Kelner, Anna Tinti, Michele Guther, Maria Lucia S. Foth, Bernardo J. Chappell, Lia Berriman, Matthew Cowling, Victoria Haigh Ferguson, Michael A. J. PLoS One Research Article 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. Public Library of Science 2018-07-24 /pmc/articles/PMC6057678/ /pubmed/30040830 http://dx.doi.org/10.1371/journal.pone.0201263 Text en © 2018 Kelner et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kelner, Anna
Tinti, Michele
Guther, Maria Lucia S.
Foth, Bernardo J.
Chappell, Lia
Berriman, Matthew
Cowling, Victoria Haigh
Ferguson, Michael A. J.
The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei
title The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei
title_full The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei
title_fullStr The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei
title_full_unstemmed The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei
title_short The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei
title_sort mrna cap methyltransferase gene tbcmt1 is not essential in vitro but is a virulence factor in vivo for bloodstream form trypanosoma brucei
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057678/
https://www.ncbi.nlm.nih.gov/pubmed/30040830
http://dx.doi.org/10.1371/journal.pone.0201263
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