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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...

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Autores principales: Forbes Beadle, Lauren, Love, Jennifer C., Shapovalova, Yuliya, Artemev, Artem, Rattray, Magnus, Ashe, Hilary L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
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.
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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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