1. Chromosomes and Gene Expression
  2. Microbiology and Infectious Disease

Codon choice directs constitutive mRNA levels in trypanosomes

  1. Janaina de Freitas Nascimento
  2. Steven Kelly
  3. Jack Sunter
  4. Mark Carrington  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. University of Oxford, United Kingdom
https://doi.org/10.7554/eLife.32467
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  1. Janaina de Freitas Nascimento
  2. Steven Kelly
  3. Jack Sunter
  4. Mark Carrington
(2018)
Codon choice directs constitutive mRNA levels in trypanosomes
eLife 7:e32467.
https://doi.org/10.7554/eLife.32467
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Abstract

Selective transcription of individual protein coding genes does not occur in trypanosomes and the cellular copy number of each mRNA must be determined post-transcriptionally. Here, we provide evidence that codon choice directs the levels of constitutively expressed mRNAs. First, a novel codon usage metric, the gene expression codon adaptation index (geCAI), was developed that maximised the relationship between codon choice and the measured abundance for a transcriptome. Second, geCAI predictions of mRNA levels were tested using differently coded GFP transgenes and were successful over a 25-fold range, similar to the variation in endogenous mRNAs. Third, translation was necessary for the accelerated mRNA turnover resulting from codon choice. Thus, in trypanosomes, the information determining the levels of most mRNAs resides in the open reading frame and translation is required to access this information.

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The following previously published data sets were used

Article and author information

Author details

  1. Janaina de Freitas Nascimento

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  2. Steven Kelly

    Department of Plant Sciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8583-5362

  3. Jack Sunter

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  4. Mark Carrington

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    mc115@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6435-7266

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

  • Janaina de Freitas Nascimento

Cambridge Overseas Trust

  • Janaina de Freitas Nascimento

Wellcome (085956/Z/08/Z)

  • Mark Carrington

Biotechnology and Biological Sciences Research Council

  • Jack Sunter

Horizon 2020 Framework Programme (637765)

  • Jack Sunter

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2018, de Freitas Nascimento et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Janaina de Freitas Nascimento
  2. Steven Kelly
  3. Jack Sunter
  4. Mark Carrington
(2018)
Codon choice directs constitutive mRNA levels in trypanosomes
eLife 7:e32467.
https://doi.org/10.7554/eLife.32467

Share this article

https://doi.org/10.7554/eLife.32467

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Further reading

    1. Microbiology and Infectious Disease

    Codon usage bias controls mRNA and protein abundance in trypanosomatids

    Laura Jeacock, Joana Faria, David Horn
    Research Article Updated

    Protein abundance differs from a few to millions of copies per cell. Trypanosoma brucei presents an excellent model for studies on codon bias and differential gene expression because transcription is broadly unregulated and uniform across the genome. T. brucei is also a major human and animal protozoal pathogen. Here, an experimental assessment, using synthetic reporter genes, revealed that GC3 codons have a major positive impact on both mRNA and protein abundance. Our estimates of relative expression, based on coding sequences alone (codon usage and sequence length), are within 2-fold of the observed values for the majority of measured cellular mRNAs (n > 7000) and proteins (n > 2000). Our estimates also correspond with expression measures from published transcriptome and proteome datasets from other trypanosomatids. We conclude that codon usage is a key factor affecting global relative mRNA and protein expression in trypanosomatids and that relative abundance can be effectively estimated using only protein coding sequences.