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Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data
Upstream open reading frames (uORFs), located in transcript leaders (5′ UTRs), are potent cis-acting regulators of translation and mRNA turnover. Recent genome-wide ribosome profiling studies suggest that thousands of uORFs initiate with non-AUG start codons. Although intriguing, these non-AUG uORF...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793785/ https://www.ncbi.nlm.nih.gov/pubmed/29254944 http://dx.doi.org/10.1101/gr.221507.117 |
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author | Spealman, Pieter Naik, Armaghan W. May, Gemma E. Kuersten, Scott Freeberg, Lindsay Murphy, Robert F. McManus, Joel |
author_facet | Spealman, Pieter Naik, Armaghan W. May, Gemma E. Kuersten, Scott Freeberg, Lindsay Murphy, Robert F. McManus, Joel |
author_sort | Spealman, Pieter |
collection | PubMed |
description | Upstream open reading frames (uORFs), located in transcript leaders (5′ UTRs), are potent cis-acting regulators of translation and mRNA turnover. Recent genome-wide ribosome profiling studies suggest that thousands of uORFs initiate with non-AUG start codons. Although intriguing, these non-AUG uORF predictions have been made without statistical control or validation; thus, the importance of these elements remains to be demonstrated. To address this, we took a comparative genomics approach to study AUG and non-AUG uORFs. We mapped transcription leaders in multiple Saccharomyces yeast species and applied a novel machine learning algorithm (uORF-seqr) to ribosome profiling data to identify statistically significant uORFs. We found that AUG and non-AUG uORFs are both frequently found in Saccharomyces yeasts. Although most non-AUG uORFs are found in only one species, hundreds have either conserved sequence or position within Saccharomyces. uORFs initiating with UUG are particularly common and are shared between species at rates similar to that of AUG uORFs. However, non-AUG uORFs are translated less efficiently than AUG-uORFs and are less subject to removal via alternative transcription initiation under normal growth conditions. These results suggest that a subset of non-AUG uORFs may play important roles in regulating gene expression. |
format | Online Article Text |
id | pubmed-5793785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57937852018-02-05 Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data Spealman, Pieter Naik, Armaghan W. May, Gemma E. Kuersten, Scott Freeberg, Lindsay Murphy, Robert F. McManus, Joel Genome Res Research Upstream open reading frames (uORFs), located in transcript leaders (5′ UTRs), are potent cis-acting regulators of translation and mRNA turnover. Recent genome-wide ribosome profiling studies suggest that thousands of uORFs initiate with non-AUG start codons. Although intriguing, these non-AUG uORF predictions have been made without statistical control or validation; thus, the importance of these elements remains to be demonstrated. To address this, we took a comparative genomics approach to study AUG and non-AUG uORFs. We mapped transcription leaders in multiple Saccharomyces yeast species and applied a novel machine learning algorithm (uORF-seqr) to ribosome profiling data to identify statistically significant uORFs. We found that AUG and non-AUG uORFs are both frequently found in Saccharomyces yeasts. Although most non-AUG uORFs are found in only one species, hundreds have either conserved sequence or position within Saccharomyces. uORFs initiating with UUG are particularly common and are shared between species at rates similar to that of AUG uORFs. However, non-AUG uORFs are translated less efficiently than AUG-uORFs and are less subject to removal via alternative transcription initiation under normal growth conditions. These results suggest that a subset of non-AUG uORFs may play important roles in regulating gene expression. Cold Spring Harbor Laboratory Press 2018-02 /pmc/articles/PMC5793785/ /pubmed/29254944 http://dx.doi.org/10.1101/gr.221507.117 Text en © 2018 Spealman et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Spealman, Pieter Naik, Armaghan W. May, Gemma E. Kuersten, Scott Freeberg, Lindsay Murphy, Robert F. McManus, Joel Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data |
title | Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data |
title_full | Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data |
title_fullStr | Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data |
title_full_unstemmed | Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data |
title_short | Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data |
title_sort | conserved non-aug uorfs revealed by a novel regression analysis of ribosome profiling data |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793785/ https://www.ncbi.nlm.nih.gov/pubmed/29254944 http://dx.doi.org/10.1101/gr.221507.117 |
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