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A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis

Alternative pre-messenger RNA splicing remodels the human transcriptome in a spatiotemporal manner during normal development and differentiation. Here we explored the landscape of transcript diversity in the erythroid lineage by RNA-seq analysis of five highly purified populations of morphologically...

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Autores principales: Pimentel, Harold, Parra, Marilyn, Gee, Sherry, Ghanem, Dana, An, Xiuli, Li, Jie, Mohandas, Narla, Pachter, Lior, Conboy, John G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973340/
https://www.ncbi.nlm.nih.gov/pubmed/24442673
http://dx.doi.org/10.1093/nar/gkt1388
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author Pimentel, Harold
Parra, Marilyn
Gee, Sherry
Ghanem, Dana
An, Xiuli
Li, Jie
Mohandas, Narla
Pachter, Lior
Conboy, John G.
author_facet Pimentel, Harold
Parra, Marilyn
Gee, Sherry
Ghanem, Dana
An, Xiuli
Li, Jie
Mohandas, Narla
Pachter, Lior
Conboy, John G.
author_sort Pimentel, Harold
collection PubMed
description Alternative pre-messenger RNA splicing remodels the human transcriptome in a spatiotemporal manner during normal development and differentiation. Here we explored the landscape of transcript diversity in the erythroid lineage by RNA-seq analysis of five highly purified populations of morphologically distinct human erythroblasts, representing the last four cell divisions before enucleation. In this unique differentiation system, we found evidence of an extensive and dynamic alternative splicing program encompassing genes with many diverse functions. Alternative splicing was particularly enriched in genes controlling cell cycle, organelle organization, chromatin function and RNA processing. Many alternative exons exhibited differentiation-associated switches in splicing efficiency, mostly in late-stage polychromatophilic and orthochromatophilic erythroblasts, in concert with extensive cellular remodeling that precedes enucleation. A subset of alternative splicing switches introduces premature translation termination codons into selected transcripts in a differentiation stage-specific manner, supporting the hypothesis that alternative splicing-coupled nonsense-mediated decay contributes to regulation of erythroid-expressed genes as a novel part of the overall differentiation program. We conclude that a highly dynamic alternative splicing program in terminally differentiating erythroblasts plays a major role in regulating gene expression to ensure synthesis of appropriate proteome at each stage as the cells remodel in preparation for production of mature red cells.
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spelling pubmed-39733402014-04-04 A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis Pimentel, Harold Parra, Marilyn Gee, Sherry Ghanem, Dana An, Xiuli Li, Jie Mohandas, Narla Pachter, Lior Conboy, John G. Nucleic Acids Res RNA Alternative pre-messenger RNA splicing remodels the human transcriptome in a spatiotemporal manner during normal development and differentiation. Here we explored the landscape of transcript diversity in the erythroid lineage by RNA-seq analysis of five highly purified populations of morphologically distinct human erythroblasts, representing the last four cell divisions before enucleation. In this unique differentiation system, we found evidence of an extensive and dynamic alternative splicing program encompassing genes with many diverse functions. Alternative splicing was particularly enriched in genes controlling cell cycle, organelle organization, chromatin function and RNA processing. Many alternative exons exhibited differentiation-associated switches in splicing efficiency, mostly in late-stage polychromatophilic and orthochromatophilic erythroblasts, in concert with extensive cellular remodeling that precedes enucleation. A subset of alternative splicing switches introduces premature translation termination codons into selected transcripts in a differentiation stage-specific manner, supporting the hypothesis that alternative splicing-coupled nonsense-mediated decay contributes to regulation of erythroid-expressed genes as a novel part of the overall differentiation program. We conclude that a highly dynamic alternative splicing program in terminally differentiating erythroblasts plays a major role in regulating gene expression to ensure synthesis of appropriate proteome at each stage as the cells remodel in preparation for production of mature red cells. Oxford University Press 2014-04 2014-01-17 /pmc/articles/PMC3973340/ /pubmed/24442673 http://dx.doi.org/10.1093/nar/gkt1388 Text en © The Author(s) 2014. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle RNA
Pimentel, Harold
Parra, Marilyn
Gee, Sherry
Ghanem, Dana
An, Xiuli
Li, Jie
Mohandas, Narla
Pachter, Lior
Conboy, John G.
A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis
title A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis
title_full A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis
title_fullStr A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis
title_full_unstemmed A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis
title_short A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis
title_sort dynamic alternative splicing program regulates gene expression during terminal erythropoiesis
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973340/
https://www.ncbi.nlm.nih.gov/pubmed/24442673
http://dx.doi.org/10.1093/nar/gkt1388
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