Translation affects mRNA stability in a codon-dependent manner in human cells
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 a...
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doaj-e0f8cb1a28e943fd991c55a041b0ea8b2021-05-05T17:33:13ZengeLife Sciences Publications LtdeLife2050-084X2019-04-01810.7554/eLife.45396Translation affects mRNA stability in a codon-dependent manner in human cellsQiushuang Wu0https://orcid.org/0000-0002-9301-3630Santiago Gerardo Medina1Gopal Kushawah2Michelle Lynn DeVore3Luciana A Castellano4Jacqelyn M Hand5Matthew Wright6Ariel Alejandro Bazzini7https://orcid.org/0000-0002-2251-5174Stowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesmRNA 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.https://elifesciences.org/articles/45396codon optimalitymRNA stabilitytranslationtRNApoly(A)-tailSLAM-seq |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qiushuang Wu Santiago Gerardo Medina Gopal Kushawah Michelle Lynn DeVore Luciana A Castellano Jacqelyn M Hand Matthew Wright Ariel Alejandro Bazzini |
spellingShingle |
Qiushuang Wu Santiago Gerardo Medina Gopal Kushawah Michelle Lynn DeVore Luciana A Castellano Jacqelyn M Hand Matthew Wright Ariel Alejandro Bazzini Translation affects mRNA stability in a codon-dependent manner in human cells eLife codon optimality mRNA stability translation tRNA poly(A)-tail SLAM-seq |
author_facet |
Qiushuang Wu Santiago Gerardo Medina Gopal Kushawah Michelle Lynn DeVore Luciana A Castellano Jacqelyn M Hand Matthew Wright Ariel Alejandro Bazzini |
author_sort |
Qiushuang Wu |
title |
Translation affects mRNA stability in a codon-dependent manner in human cells |
title_short |
Translation affects mRNA stability in a codon-dependent manner in human cells |
title_full |
Translation affects mRNA stability in a codon-dependent manner in human cells |
title_fullStr |
Translation affects mRNA stability in a codon-dependent manner in human cells |
title_full_unstemmed |
Translation affects mRNA stability in a codon-dependent manner in human cells |
title_sort |
translation affects mrna stability in a codon-dependent manner in human cells |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-04-01 |
description |
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. |
topic |
codon optimality mRNA stability translation tRNA poly(A)-tail SLAM-seq |
url |
https://elifesciences.org/articles/45396 |
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