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A novel translational control mechanism involving RNA structures within coding sequences
The impact of RNA structures in coding sequences (CDS) within mRNAs is poorly understood. Here, we identify a novel and highly conserved mechanism of translational control involving RNA structures within coding sequences and the DEAD-box helicase Dhh1. Using yeast genetics and genome-wide ribosome p...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204348/ https://www.ncbi.nlm.nih.gov/pubmed/27821408 http://dx.doi.org/10.1101/gr.209015.116 |
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author | Jungfleisch, Jennifer Nedialkova, Danny D. Dotu, Ivan Sloan, Katherine E. Martinez-Bosch, Neus Brüning, Lukas Raineri, Emanuele Navarro, Pilar Bohnsack, Markus T. Leidel, Sebastian A. Díez, Juana |
author_facet | Jungfleisch, Jennifer Nedialkova, Danny D. Dotu, Ivan Sloan, Katherine E. Martinez-Bosch, Neus Brüning, Lukas Raineri, Emanuele Navarro, Pilar Bohnsack, Markus T. Leidel, Sebastian A. Díez, Juana |
author_sort | Jungfleisch, Jennifer |
collection | PubMed |
description | The impact of RNA structures in coding sequences (CDS) within mRNAs is poorly understood. Here, we identify a novel and highly conserved mechanism of translational control involving RNA structures within coding sequences and the DEAD-box helicase Dhh1. Using yeast genetics and genome-wide ribosome profiling analyses, we show that this mechanism, initially derived from studies of the Brome Mosaic virus RNA genome, extends to yeast and human mRNAs highly enriched in membrane and secreted proteins. All Dhh1-dependent mRNAs, viral and cellular, share key common features. First, they contain long and highly structured CDSs, including a region located around nucleotide 70 after the translation initiation site; second, they are directly bound by Dhh1 with a specific binding distribution; and third, complementary experimental approaches suggest that they are activated by Dhh1 at the translation initiation step. Our results show that ribosome translocation is not the only unwinding force of CDS and uncover a novel layer of translational control that involves RNA helicases and RNA folding within CDS providing novel opportunities for regulation of membrane and secretome proteins. |
format | Online Article Text |
id | pubmed-5204348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-52043482017-07-01 A novel translational control mechanism involving RNA structures within coding sequences Jungfleisch, Jennifer Nedialkova, Danny D. Dotu, Ivan Sloan, Katherine E. Martinez-Bosch, Neus Brüning, Lukas Raineri, Emanuele Navarro, Pilar Bohnsack, Markus T. Leidel, Sebastian A. Díez, Juana Genome Res Research The impact of RNA structures in coding sequences (CDS) within mRNAs is poorly understood. Here, we identify a novel and highly conserved mechanism of translational control involving RNA structures within coding sequences and the DEAD-box helicase Dhh1. Using yeast genetics and genome-wide ribosome profiling analyses, we show that this mechanism, initially derived from studies of the Brome Mosaic virus RNA genome, extends to yeast and human mRNAs highly enriched in membrane and secreted proteins. All Dhh1-dependent mRNAs, viral and cellular, share key common features. First, they contain long and highly structured CDSs, including a region located around nucleotide 70 after the translation initiation site; second, they are directly bound by Dhh1 with a specific binding distribution; and third, complementary experimental approaches suggest that they are activated by Dhh1 at the translation initiation step. Our results show that ribosome translocation is not the only unwinding force of CDS and uncover a novel layer of translational control that involves RNA helicases and RNA folding within CDS providing novel opportunities for regulation of membrane and secretome proteins. Cold Spring Harbor Laboratory Press 2017-01 /pmc/articles/PMC5204348/ /pubmed/27821408 http://dx.doi.org/10.1101/gr.209015.116 Text en © 2017 Jungfleisch et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Jungfleisch, Jennifer Nedialkova, Danny D. Dotu, Ivan Sloan, Katherine E. Martinez-Bosch, Neus Brüning, Lukas Raineri, Emanuele Navarro, Pilar Bohnsack, Markus T. Leidel, Sebastian A. Díez, Juana A novel translational control mechanism involving RNA structures within coding sequences |
title | A novel translational control mechanism involving RNA structures within coding sequences |
title_full | A novel translational control mechanism involving RNA structures within coding sequences |
title_fullStr | A novel translational control mechanism involving RNA structures within coding sequences |
title_full_unstemmed | A novel translational control mechanism involving RNA structures within coding sequences |
title_short | A novel translational control mechanism involving RNA structures within coding sequences |
title_sort | novel translational control mechanism involving rna structures within coding sequences |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204348/ https://www.ncbi.nlm.nih.gov/pubmed/27821408 http://dx.doi.org/10.1101/gr.209015.116 |
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