1. Chromosomes and Gene Expression
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Translation affects mRNA stability in a codon dependent manner in human cells

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Cite this article as: eLife 2019;8:e45396 doi: 10.7554/eLife.45396

Abstract

mRNA translation decodes nucleotide into amino acid sequences. However, translation has also been shown to affect mRNA stability depending on codon composition in model organisms, although universality of this mechanism remains unclear. Here, using three independent approaches to measure exogenous and endogenous mRNA decay, we define which codons are associated with stable or unstable mRNAs in human cells. We demonstrate that the regulatory information affecting mRNA stability is encoded in codons and not in nucleotides. Stabilizing codons tend to be associated with higher tRNA levels and higher charged/total tRNA ratios. While mRNAs enriched in destabilizing codons tend to possess shorter poly(A)-tails, the poly(A)-tail is not required for the codon-mediated mRNA stability. This mechanism depends on translation; however, the number of ribosome loads into a mRNA modulates the codon-mediated effects on gene expression. This work provides definitive evidence that translation strongly affects mRNA stability in a codon-dependent manner in human cells.

Data availability

The following datasets have been uploaded to NCBI GSE, under the accession number GSE126523.Endogenous mRNA decay:1.293T: 0h, 0h, 1h, 2h,3h,6h,6h2.Hela: 0h,0h,1h,2h,3h,4h,5h,6h,6h3.RPE: 0h,0h,1h,2h,3h,4h,5h,6h,6hORFome:1.293t: 0h, 0h, 1h, 1h, 2h, 2h, 3h, 3h, 4h, 4h, 5h, 5h, 6h, 6h2.K562: 0h, 0h, 1h, 1h, 2h, 2h, 3h, 3h, 4h, 4h, 5h, 5h, 6h, 6hSLAM-seq:1.K562: 0h, 0h, 0h, 2h, 2h, 2h, 4h, 4h, 4h, 6h, 6h, 6h

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Qiushuang Wu

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Santiago Gerardo Medina

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Gopal Kushawah

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michelle Lynn DeVore

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Luciana A Castellano

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jacqelyn M Hand

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Matthew Wright

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Ariel Alejandro Bazzini

    Stowers Institute for Medical Research, Kansas City, United States
    For correspondence
    arb@stowers.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2251-5174

Funding

Stowers Institute for Medical Research

  • Ariel Alejandro Bazzini

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the zebrafish were handled according to approved institutional animal care and use committee (IACUC) protocols (#2016-0159) of the Stowers Institute for Medical Research. The protocol was approved on August 18th 2018.

Reviewing Editor

  1. Nahum Sonenberg, McGill University, Canada

Publication history

  1. Received: January 21, 2019
  2. Accepted: April 20, 2019
  3. Accepted Manuscript published: April 23, 2019 (version 1)
  4. Version of Record published: May 21, 2019 (version 2)

Copyright

© 2019, Wu 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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