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

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.

Data availability

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.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Publication history

  1. Received: October 3, 2017
  2. Accepted: February 27, 2018
  3. Accepted Manuscript published: March 15, 2018 (version 1)
  4. Version of Record published: April 11, 2018 (version 2)

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
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