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The landscape of alternative polyadenylation in single cells of the developing mouse embryo

3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poor...

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Autores principales: Agarwal, Vikram, Lopez-Darwin, Sereno, Kelley, David R., Shendure, Jay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385098/
https://www.ncbi.nlm.nih.gov/pubmed/34429411
http://dx.doi.org/10.1038/s41467-021-25388-8
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author Agarwal, Vikram
Lopez-Darwin, Sereno
Kelley, David R.
Shendure, Jay
author_facet Agarwal, Vikram
Lopez-Darwin, Sereno
Kelley, David R.
Shendure, Jay
author_sort Agarwal, Vikram
collection PubMed
description 3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examine a dataset comprising ~2 million nuclei spanning E9.5–E13.5 of mouse embryonic development to quantify transcriptome-wide changes in alternative polyadenylation (APA). We observe a global lengthening of 3′ UTRs across embryonic stages in all cell types, although we detect shorter 3′ UTRs in hematopoietic lineages and longer 3′ UTRs in neuronal cell types within each stage. An analysis of RNA-binding protein (RBP) dynamics identifies ELAV-like family members, which are concomitantly induced in neuronal lineages and developmental stages experiencing 3′-UTR lengthening, as putative regulators of APA. By measuring 3′-UTR isoforms in an expansive single cell dataset, our work provides a transcriptome-wide and organism-wide map of the dynamic landscape of alternative polyadenylation during mammalian organogenesis.
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spelling pubmed-83850982021-09-22 The landscape of alternative polyadenylation in single cells of the developing mouse embryo Agarwal, Vikram Lopez-Darwin, Sereno Kelley, David R. Shendure, Jay Nat Commun Article 3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examine a dataset comprising ~2 million nuclei spanning E9.5–E13.5 of mouse embryonic development to quantify transcriptome-wide changes in alternative polyadenylation (APA). We observe a global lengthening of 3′ UTRs across embryonic stages in all cell types, although we detect shorter 3′ UTRs in hematopoietic lineages and longer 3′ UTRs in neuronal cell types within each stage. An analysis of RNA-binding protein (RBP) dynamics identifies ELAV-like family members, which are concomitantly induced in neuronal lineages and developmental stages experiencing 3′-UTR lengthening, as putative regulators of APA. By measuring 3′-UTR isoforms in an expansive single cell dataset, our work provides a transcriptome-wide and organism-wide map of the dynamic landscape of alternative polyadenylation during mammalian organogenesis. Nature Publishing Group UK 2021-08-24 /pmc/articles/PMC8385098/ /pubmed/34429411 http://dx.doi.org/10.1038/s41467-021-25388-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Agarwal, Vikram
Lopez-Darwin, Sereno
Kelley, David R.
Shendure, Jay
The landscape of alternative polyadenylation in single cells of the developing mouse embryo
title The landscape of alternative polyadenylation in single cells of the developing mouse embryo
title_full The landscape of alternative polyadenylation in single cells of the developing mouse embryo
title_fullStr The landscape of alternative polyadenylation in single cells of the developing mouse embryo
title_full_unstemmed The landscape of alternative polyadenylation in single cells of the developing mouse embryo
title_short The landscape of alternative polyadenylation in single cells of the developing mouse embryo
title_sort landscape of alternative polyadenylation in single cells of the developing mouse embryo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385098/
https://www.ncbi.nlm.nih.gov/pubmed/34429411
http://dx.doi.org/10.1038/s41467-021-25388-8
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