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Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast

BACKGROUND: The control of gene expression in eukaryotic cells occurs both transcriptionally and post-transcriptionally. Although many genes are now known to be regulated at the translational level, in general, the mechanisms are poorly understood. We have previously presented polysomal gradient and...

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Autores principales: Lawless, Craig, Pearson, Richard D, Selley, Julian N, Smirnova, Julia B, Grant, Christopher M, Ashe, Mark P, Pavitt, Graham D, Hubbard, Simon J
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649001/
https://www.ncbi.nlm.nih.gov/pubmed/19128476
http://dx.doi.org/10.1186/1471-2164-10-7
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author Lawless, Craig
Pearson, Richard D
Selley, Julian N
Smirnova, Julia B
Grant, Christopher M
Ashe, Mark P
Pavitt, Graham D
Hubbard, Simon J
author_facet Lawless, Craig
Pearson, Richard D
Selley, Julian N
Smirnova, Julia B
Grant, Christopher M
Ashe, Mark P
Pavitt, Graham D
Hubbard, Simon J
author_sort Lawless, Craig
collection PubMed
description BACKGROUND: The control of gene expression in eukaryotic cells occurs both transcriptionally and post-transcriptionally. Although many genes are now known to be regulated at the translational level, in general, the mechanisms are poorly understood. We have previously presented polysomal gradient and array-based evidence that translational control is widespread in a significant number of genes when yeast cells are exposed to a range of stresses. Here we have re-examined these gene sets, considering the role of UTR sequences in the translational responses of these genes using recent large-scale datasets which define 5' and 3' transcriptional ends for many yeast genes. In particular, we highlight the potential role of 5' UTRs and upstream open reading frames (uORFs). RESULTS: We show a highly significant enrichment in specific GO functional classes for genes that are translationally up- and down-regulated under given stresses (e.g. carbohydrate metabolism is up-regulated under amino acid starvation). Cross-referencing these data with the stress response data we show that translationally upregulated genes have longer 5' UTRs, consistent with their role in translational regulation. In the first genome-wide study of uORFs in a set of mapped 5' UTRs, we show that uORFs are rare, being statistically under-represented in UTR sequences. However, they have distinct compositional biases consistent with their putative role in translational control and are more common in genes which are apparently translationally up-regulated. CONCLUSION: These results demonstrate a central regulatory role for UTR sequences, and 5' UTRs in particular, highlighting the significant role of uORFs in post-transcriptional control in yeast. Yeast uORFs are more highly conserved than has been suggested, lending further weight to their significance as functional elements involved in gene regulation. It also suggests a more complex and novel mechanism of control, whereby uORFs permit genes to escape from a more general attenuation of translation under conditions of stress. However, since uORFs are relatively rare (only ~13% of yeast genes have them) there remain many unanswered questions as to how UTR elements can direct translational control of many hundreds of genes under stress.
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spelling pubmed-26490012009-02-28 Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast Lawless, Craig Pearson, Richard D Selley, Julian N Smirnova, Julia B Grant, Christopher M Ashe, Mark P Pavitt, Graham D Hubbard, Simon J BMC Genomics Research Article BACKGROUND: The control of gene expression in eukaryotic cells occurs both transcriptionally and post-transcriptionally. Although many genes are now known to be regulated at the translational level, in general, the mechanisms are poorly understood. We have previously presented polysomal gradient and array-based evidence that translational control is widespread in a significant number of genes when yeast cells are exposed to a range of stresses. Here we have re-examined these gene sets, considering the role of UTR sequences in the translational responses of these genes using recent large-scale datasets which define 5' and 3' transcriptional ends for many yeast genes. In particular, we highlight the potential role of 5' UTRs and upstream open reading frames (uORFs). RESULTS: We show a highly significant enrichment in specific GO functional classes for genes that are translationally up- and down-regulated under given stresses (e.g. carbohydrate metabolism is up-regulated under amino acid starvation). Cross-referencing these data with the stress response data we show that translationally upregulated genes have longer 5' UTRs, consistent with their role in translational regulation. In the first genome-wide study of uORFs in a set of mapped 5' UTRs, we show that uORFs are rare, being statistically under-represented in UTR sequences. However, they have distinct compositional biases consistent with their putative role in translational control and are more common in genes which are apparently translationally up-regulated. CONCLUSION: These results demonstrate a central regulatory role for UTR sequences, and 5' UTRs in particular, highlighting the significant role of uORFs in post-transcriptional control in yeast. Yeast uORFs are more highly conserved than has been suggested, lending further weight to their significance as functional elements involved in gene regulation. It also suggests a more complex and novel mechanism of control, whereby uORFs permit genes to escape from a more general attenuation of translation under conditions of stress. However, since uORFs are relatively rare (only ~13% of yeast genes have them) there remain many unanswered questions as to how UTR elements can direct translational control of many hundreds of genes under stress. BioMed Central 2009-01-07 /pmc/articles/PMC2649001/ /pubmed/19128476 http://dx.doi.org/10.1186/1471-2164-10-7 Text en Copyright © 2009 Lawless et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lawless, Craig
Pearson, Richard D
Selley, Julian N
Smirnova, Julia B
Grant, Christopher M
Ashe, Mark P
Pavitt, Graham D
Hubbard, Simon J
Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast
title Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast
title_full Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast
title_fullStr Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast
title_full_unstemmed Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast
title_short Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast
title_sort upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649001/
https://www.ncbi.nlm.nih.gov/pubmed/19128476
http://dx.doi.org/10.1186/1471-2164-10-7
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