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Measuring mRNA Levels Over Time During the Yeast S. cerevisiae Hypoxic Response
Published on: August 10, 2017
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Codon choice directs constitutive mRNA levels in trypanosomes.
Janaina de Freitas Nascimento1, Steven Kelly2, Jack Sunter1
1Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Elife
|March 16, 2018
Summary
In trypanosomes, codon choice, not selective transcription, determines mRNA levels. This study introduces a new metric (geCAI) showing translation is required to regulate mRNA abundance via codon selection within the open reading frame.
Area of Science:
- Molecular Biology
- Genetics
- Parasitology
Background:
- Selective transcription of protein-coding genes is absent in trypanosomes.
- mRNA abundance is regulated post-transcriptionally in these organisms.
Purpose of the Study:
- To investigate the role of codon choice in determining mRNA levels in trypanosomes.
- To develop a metric correlating codon usage with mRNA abundance.
- To confirm the necessity of translation for codon-driven mRNA regulation.
Main Methods:
- Development of a novel codon usage metric, the gene expression codon adaptation index (geCAI).
- Testing geCAI predictions using transgenes encoding GFP with varied codon usage.
- Assessing the impact of translation inhibition on codon-mediated mRNA turnover.
Main Results:
- The geCAI metric effectively correlated codon choice with measured mRNA abundance across a transcriptome.
- geCAI accurately predicted mRNA levels for GFP transgenes over a 25-fold range.
- Accelerated mRNA turnover due to codon choice was dependent on ongoing translation.
Conclusions:
- Codon choice within the open reading frame is a primary determinant of mRNA levels in trypanosomes.
- Translation is essential for accessing and acting upon the information encoded in codon usage to regulate mRNA stability.
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