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Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5′ to 3′ degradation
Regulation of mRNA degradation is critical for a diverse array of cellular processes and developmental cell fate decisions. Many methods for determining mRNA half-lives rely on transcriptional inhibition or metabolic labelling. Here, we use a non-invasive method for estimating half-lives for hundred...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882958/ https://www.ncbi.nlm.nih.gov/pubmed/36649329 http://dx.doi.org/10.1371/journal.pbio.3001956 |
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author | Forbes Beadle, Lauren Love, Jennifer C. Shapovalova, Yuliya Artemev, Artem Rattray, Magnus Ashe, Hilary L. |
author_facet | Forbes Beadle, Lauren Love, Jennifer C. Shapovalova, Yuliya Artemev, Artem Rattray, Magnus Ashe, Hilary L. |
author_sort | Forbes Beadle, Lauren |
collection | PubMed |
description | Regulation of mRNA degradation is critical for a diverse array of cellular processes and developmental cell fate decisions. Many methods for determining mRNA half-lives rely on transcriptional inhibition or metabolic labelling. Here, we use a non-invasive method for estimating half-lives for hundreds of mRNAs in the early Drosophila embryo. This approach uses the intronic and exonic reads from a total RNA-seq time series and Gaussian process regression to model the dynamics of premature and mature mRNAs. We show how regulation of mRNA stability is used to establish a range of mature mRNA dynamics during embryogenesis, despite shared transcription profiles. Using single-molecule imaging, we provide evidence that, for the mRNAs tested, there is a correlation between short half-life and mRNA association with P-bodies. Moreover, we detect an enrichment of mRNA 3′ ends in P-bodies in the early embryo, consistent with 5′ to 3′ degradation occurring in P-bodies for at least a subset of mRNAs. We discuss our findings in relation to recently published data suggesting that the primary function of P-bodies in other biological contexts is mRNA storage. |
format | Online Article Text |
id | pubmed-9882958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-98829582023-01-28 Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5′ to 3′ degradation Forbes Beadle, Lauren Love, Jennifer C. Shapovalova, Yuliya Artemev, Artem Rattray, Magnus Ashe, Hilary L. PLoS Biol Research Article Regulation of mRNA degradation is critical for a diverse array of cellular processes and developmental cell fate decisions. Many methods for determining mRNA half-lives rely on transcriptional inhibition or metabolic labelling. Here, we use a non-invasive method for estimating half-lives for hundreds of mRNAs in the early Drosophila embryo. This approach uses the intronic and exonic reads from a total RNA-seq time series and Gaussian process regression to model the dynamics of premature and mature mRNAs. We show how regulation of mRNA stability is used to establish a range of mature mRNA dynamics during embryogenesis, despite shared transcription profiles. Using single-molecule imaging, we provide evidence that, for the mRNAs tested, there is a correlation between short half-life and mRNA association with P-bodies. Moreover, we detect an enrichment of mRNA 3′ ends in P-bodies in the early embryo, consistent with 5′ to 3′ degradation occurring in P-bodies for at least a subset of mRNAs. We discuss our findings in relation to recently published data suggesting that the primary function of P-bodies in other biological contexts is mRNA storage. Public Library of Science 2023-01-17 /pmc/articles/PMC9882958/ /pubmed/36649329 http://dx.doi.org/10.1371/journal.pbio.3001956 Text en © 2023 Forbes Beadle et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Forbes Beadle, Lauren Love, Jennifer C. Shapovalova, Yuliya Artemev, Artem Rattray, Magnus Ashe, Hilary L. Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5′ to 3′ degradation |
title | Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5′ to 3′ degradation |
title_full | Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5′ to 3′ degradation |
title_fullStr | Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5′ to 3′ degradation |
title_full_unstemmed | Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5′ to 3′ degradation |
title_short | Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5′ to 3′ degradation |
title_sort | combined modelling of mrna decay dynamics and single-molecule imaging in the drosophila embryo uncovers a role for p-bodies in 5′ to 3′ degradation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882958/ https://www.ncbi.nlm.nih.gov/pubmed/36649329 http://dx.doi.org/10.1371/journal.pbio.3001956 |
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