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Temperature-dependent regulation of upstream open reading frame translation in S. cerevisiae
BACKGROUND: Translation of an mRNA in eukaryotes starts at an AUG codon in most cases, but near-cognate codons (NCCs) such as UUG, ACG, and AUU can also be used as start sites at low levels in Saccharomyces cerevisiae. Initiation from NCCs or AUGs in the 5′-untranslated regions (UTRs) of mRNAs can l...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898956/ https://www.ncbi.nlm.nih.gov/pubmed/31810458 http://dx.doi.org/10.1186/s12915-019-0718-5 |
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author | Kulkarni, Shardul D. Zhou, Fujun Sen, Neelam Dabas Zhang, Hongen Hinnebusch, Alan G. Lorsch, Jon R. |
author_facet | Kulkarni, Shardul D. Zhou, Fujun Sen, Neelam Dabas Zhang, Hongen Hinnebusch, Alan G. Lorsch, Jon R. |
author_sort | Kulkarni, Shardul D. |
collection | PubMed |
description | BACKGROUND: Translation of an mRNA in eukaryotes starts at an AUG codon in most cases, but near-cognate codons (NCCs) such as UUG, ACG, and AUU can also be used as start sites at low levels in Saccharomyces cerevisiae. Initiation from NCCs or AUGs in the 5′-untranslated regions (UTRs) of mRNAs can lead to translation of upstream open reading frames (uORFs) that might regulate expression of the main ORF (mORF). Although there is some circumstantial evidence that the translation of uORFs can be affected by environmental conditions, little is known about how it is affected by changes in growth temperature. RESULTS: Using reporter assays, we found that changes in growth temperature can affect translation from NCC start sites in yeast cells, suggesting the possibility that gene expression could be regulated by temperature by altering use of different uORF start codons. Using ribosome profiling, we provide evidence that growth temperature regulates the efficiency of translation of nearly 200 uORFs in S. cerevisiae. Of these uORFs, most that start with an AUG codon have increased translational efficiency at 37 °C relative to 30 °C and decreased efficiency at 20 °C. For translationally regulated uORFs starting with NCCs, we did not observe a general trend for the direction of regulation as a function of temperature, suggesting mRNA-specific features can determine the mode of temperature-dependent regulation. Consistent with this conclusion, the position of the uORFs in the 5′-leader relative to the 5′-cap and the start codon of the main ORF correlates with the direction of temperature-dependent regulation of uORF translation. We have identified several novel cases in which changes in uORF translation are inversely correlated with changes in the translational efficiency of the downstream main ORF. Our data suggest that translation of these mRNAs is subject to temperature-dependent, uORF-mediated regulation. CONCLUSIONS: Our data suggest that alterations in the translation of specific uORFs by temperature can regulate gene expression in S. cerevisiae. |
format | Online Article Text |
id | pubmed-6898956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68989562019-12-11 Temperature-dependent regulation of upstream open reading frame translation in S. cerevisiae Kulkarni, Shardul D. Zhou, Fujun Sen, Neelam Dabas Zhang, Hongen Hinnebusch, Alan G. Lorsch, Jon R. BMC Biol Research Article BACKGROUND: Translation of an mRNA in eukaryotes starts at an AUG codon in most cases, but near-cognate codons (NCCs) such as UUG, ACG, and AUU can also be used as start sites at low levels in Saccharomyces cerevisiae. Initiation from NCCs or AUGs in the 5′-untranslated regions (UTRs) of mRNAs can lead to translation of upstream open reading frames (uORFs) that might regulate expression of the main ORF (mORF). Although there is some circumstantial evidence that the translation of uORFs can be affected by environmental conditions, little is known about how it is affected by changes in growth temperature. RESULTS: Using reporter assays, we found that changes in growth temperature can affect translation from NCC start sites in yeast cells, suggesting the possibility that gene expression could be regulated by temperature by altering use of different uORF start codons. Using ribosome profiling, we provide evidence that growth temperature regulates the efficiency of translation of nearly 200 uORFs in S. cerevisiae. Of these uORFs, most that start with an AUG codon have increased translational efficiency at 37 °C relative to 30 °C and decreased efficiency at 20 °C. For translationally regulated uORFs starting with NCCs, we did not observe a general trend for the direction of regulation as a function of temperature, suggesting mRNA-specific features can determine the mode of temperature-dependent regulation. Consistent with this conclusion, the position of the uORFs in the 5′-leader relative to the 5′-cap and the start codon of the main ORF correlates with the direction of temperature-dependent regulation of uORF translation. We have identified several novel cases in which changes in uORF translation are inversely correlated with changes in the translational efficiency of the downstream main ORF. Our data suggest that translation of these mRNAs is subject to temperature-dependent, uORF-mediated regulation. CONCLUSIONS: Our data suggest that alterations in the translation of specific uORFs by temperature can regulate gene expression in S. cerevisiae. BioMed Central 2019-12-06 /pmc/articles/PMC6898956/ /pubmed/31810458 http://dx.doi.org/10.1186/s12915-019-0718-5 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Kulkarni, Shardul D. Zhou, Fujun Sen, Neelam Dabas Zhang, Hongen Hinnebusch, Alan G. Lorsch, Jon R. Temperature-dependent regulation of upstream open reading frame translation in S. cerevisiae |
title | Temperature-dependent regulation of upstream open reading frame translation in S. cerevisiae |
title_full | Temperature-dependent regulation of upstream open reading frame translation in S. cerevisiae |
title_fullStr | Temperature-dependent regulation of upstream open reading frame translation in S. cerevisiae |
title_full_unstemmed | Temperature-dependent regulation of upstream open reading frame translation in S. cerevisiae |
title_short | Temperature-dependent regulation of upstream open reading frame translation in S. cerevisiae |
title_sort | temperature-dependent regulation of upstream open reading frame translation in s. cerevisiae |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898956/ https://www.ncbi.nlm.nih.gov/pubmed/31810458 http://dx.doi.org/10.1186/s12915-019-0718-5 |
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