Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
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
_version_ 1782489883173978112
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
work_keys_str_mv AT jungfleischjennifer anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT nedialkovadannyd anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT dotuivan anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT sloankatherinee anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT martinezboschneus anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT bruninglukas anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT raineriemanuele anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT navarropilar anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT bohnsackmarkust anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT leidelsebastiana anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT diezjuana anoveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT jungfleischjennifer noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT nedialkovadannyd noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT dotuivan noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT sloankatherinee noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT martinezboschneus noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT bruninglukas noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT raineriemanuele noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT navarropilar noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT bohnsackmarkust noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT leidelsebastiana noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences
AT diezjuana noveltranslationalcontrolmechanisminvolvingrnastructureswithincodingsequences