Cargando…
Single-molecule imaging reveals translation-dependent destabilization of mRNAs
The relationship between mRNA translation and decay is incompletely understood, with conflicting reports suggesting that translation can either promote decay or stabilize mRNAs. The effect of translation on mRNA decay has mainly been studied using ensemble measurements and global transcription and t...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9957601/ https://www.ncbi.nlm.nih.gov/pubmed/36731471 http://dx.doi.org/10.1016/j.molcel.2023.01.013 |
_version_ | 1784894863622275072 |
---|---|
author | Dave, Pratik Roth, Gregory Griesbach, Esther Mateju, Daniel Hochstoeger, Tobias Chao, Jeffrey A. |
author_facet | Dave, Pratik Roth, Gregory Griesbach, Esther Mateju, Daniel Hochstoeger, Tobias Chao, Jeffrey A. |
author_sort | Dave, Pratik |
collection | PubMed |
description | The relationship between mRNA translation and decay is incompletely understood, with conflicting reports suggesting that translation can either promote decay or stabilize mRNAs. The effect of translation on mRNA decay has mainly been studied using ensemble measurements and global transcription and translation inhibitors, which can have pleiotropic effects. We developed a single-molecule imaging approach to control the translation of a specific transcript that enabled simultaneous measurement of translation and mRNA decay. Our results demonstrate that mRNA translation reduces mRNA stability, and mathematical modeling suggests that this process is dependent on ribosome flux. Furthermore, our results indicate that miRNAs mediate efficient degradation of both translating and non-translating target mRNAs and reveal a predominant role for mRNA degradation in miRNA-mediated regulation. Simultaneous observation of translation and decay of single mRNAs provides a framework to directly study how these processes are interconnected in cells. |
format | Online Article Text |
id | pubmed-9957601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-99576012023-02-25 Single-molecule imaging reveals translation-dependent destabilization of mRNAs Dave, Pratik Roth, Gregory Griesbach, Esther Mateju, Daniel Hochstoeger, Tobias Chao, Jeffrey A. Mol Cell Article The relationship between mRNA translation and decay is incompletely understood, with conflicting reports suggesting that translation can either promote decay or stabilize mRNAs. The effect of translation on mRNA decay has mainly been studied using ensemble measurements and global transcription and translation inhibitors, which can have pleiotropic effects. We developed a single-molecule imaging approach to control the translation of a specific transcript that enabled simultaneous measurement of translation and mRNA decay. Our results demonstrate that mRNA translation reduces mRNA stability, and mathematical modeling suggests that this process is dependent on ribosome flux. Furthermore, our results indicate that miRNAs mediate efficient degradation of both translating and non-translating target mRNAs and reveal a predominant role for mRNA degradation in miRNA-mediated regulation. Simultaneous observation of translation and decay of single mRNAs provides a framework to directly study how these processes are interconnected in cells. Cell Press 2023-02-16 /pmc/articles/PMC9957601/ /pubmed/36731471 http://dx.doi.org/10.1016/j.molcel.2023.01.013 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Dave, Pratik Roth, Gregory Griesbach, Esther Mateju, Daniel Hochstoeger, Tobias Chao, Jeffrey A. Single-molecule imaging reveals translation-dependent destabilization of mRNAs |
title | Single-molecule imaging reveals translation-dependent destabilization of mRNAs |
title_full | Single-molecule imaging reveals translation-dependent destabilization of mRNAs |
title_fullStr | Single-molecule imaging reveals translation-dependent destabilization of mRNAs |
title_full_unstemmed | Single-molecule imaging reveals translation-dependent destabilization of mRNAs |
title_short | Single-molecule imaging reveals translation-dependent destabilization of mRNAs |
title_sort | single-molecule imaging reveals translation-dependent destabilization of mrnas |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9957601/ https://www.ncbi.nlm.nih.gov/pubmed/36731471 http://dx.doi.org/10.1016/j.molcel.2023.01.013 |
work_keys_str_mv | AT davepratik singlemoleculeimagingrevealstranslationdependentdestabilizationofmrnas AT rothgregory singlemoleculeimagingrevealstranslationdependentdestabilizationofmrnas AT griesbachesther singlemoleculeimagingrevealstranslationdependentdestabilizationofmrnas AT matejudaniel singlemoleculeimagingrevealstranslationdependentdestabilizationofmrnas AT hochstoegertobias singlemoleculeimagingrevealstranslationdependentdestabilizationofmrnas AT chaojeffreya singlemoleculeimagingrevealstranslationdependentdestabilizationofmrnas |