In:
eLife, eLife Sciences Publications, Ltd, Vol. 4 ( 2015-01-26)
Abstract:
Proteins carry out essential tasks for living cells and genes contain the instructions to make proteins within their DNA. These instructions are copied to make a molecule of mRNA, and a molecular machine known as a ribosome then reads and translates the mRNA to build the protein. The first step in the translation process is called ‘initiation’ and requires a protein called eIF2 to work together with the ribosome. This step involves identifying an instruction called the start codon that marks the beginning of the mRNA's coding sequence. The section of an mRNA molecule before the start codon is not normally translated by the ribosome and is hence called the 5′ untranslated region. Building proteins requires energy and resources, and so it is carefully regulated. If a cell is stressed, such as by being exposed to harmful chemicals, it makes fewer proteins in order to conserve its resources. This down-regulation of protein production is achieved in part by the cell chemically modifying its eIF2 proteins to make them less able to initiate translation. However, stressed cells still continue to make more of certain proteins that help them to combat stress. The mRNA molecules for some of these proteins contain at least one other start codon in the 5′ untranslated region. The sequence that would be translated from such a start codon is known as an upstream open reading frame (or uORF for short)—and this feature is thought to help certain proteins to still be expressed despite low levels of active eIF2. Andreev, O'Connor et al. have now analysed which mRNAs are translated in human cells that have been treated with a chemical that induces stress and makes the eIF2 protein less able to initiate translation. To do so, a technique called ribosome profiling was used to identify all of the mRNA molecules bound to ribosomes shortly after treatment with this chemical. Overall translation of most mRNAs in stressed cells was reduced to a quarter of the normal level. However, Andreev, O'Connor et al. observed that the translation of a few mRNAs continued almost as normal, or even increased, after the chemical treatment. Notably, most of these mRNAs encoded regulatory proteins, which are not required in large amounts. With one exception, all of these resistant mRNAs contained uORFs. In unstressed cells, these uORFs were efficiently translated, while the same mRNA's coding sequences were translated less efficiently. Andreev, O'Connor et al. suggest that these two features could be used to identify mRNAs that are still translated into working proteins when cells are stressed. Further work is now needed to explore the mechanisms by which translation of these uORFs allows mRNAs to resist the stress.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.03971.001
DOI:
10.7554/eLife.03971.002
DOI:
10.7554/eLife.03971.003
DOI:
10.7554/eLife.03971.004
DOI:
10.7554/eLife.03971.005
DOI:
10.7554/eLife.03971.006
DOI:
10.7554/eLife.03971.007
DOI:
10.7554/eLife.03971.008
DOI:
10.7554/eLife.03971.009
DOI:
10.7554/eLife.03971.010
DOI:
10.7554/eLife.03971.011
DOI:
10.7554/eLife.03971.012
DOI:
10.7554/eLife.03971.013
DOI:
10.7554/eLife.03971.014
DOI:
10.7554/eLife.03971.015
DOI:
10.7554/eLife.03971.016
DOI:
10.7554/eLife.03971.017
DOI:
10.7554/eLife.03971.018
DOI:
10.7554/eLife.03971.019
DOI:
10.7554/eLife.03971.020
DOI:
10.7554/eLife.03971.021
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2015
detail.hit.zdb_id:
2687154-3
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