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A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis

Pimentel, Harold and Parra, Marilynn and Gee, Sherry and Ghanem, Dana and An, Xiuli and Li, Jie and Mohandas, Narla and Pachter, Lior and Conboy, John G. (2014) A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis. Nucleic Acids Research, 42 (6). pp. 4031-4042. ISSN 0305-1048. PMCID PMC3973340. doi:10.1093/nar/gkt1388.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle
Li, Jie0000-0002-3733-4587
Pachter, Lior0000-0002-9164-6231
Additional Information:© The Author(s) 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. Received October 29, 2013; Revised December 16, 2013; Accepted December 17, 2013. J.G.C., L.P., N.M. and X.A. designed the research; H.P., M.P., S.L.G., D.G. and J.L. performed research and analyzed data; and J.G.C., N.M., X.A., L.P. and H.P. wrote the article. FUNDING: The National Institutes of Health (NIH) [DK094699 and DK032094]. Director, Office of Science, and Office of Biological & Environmental Research of the US Department of Energy under Contract No. DE-AC02-05CH1123. Funding for open access charge: NIH [DK094699]. Conflict of interest statement. None declared.
Funding AgencyGrant Number
Department of Energy (DOE)DE-AC02-05CH11231
Issue or Number:6
PubMed Central ID:PMC3973340
Record Number:CaltechAUTHORS:20170303-143819723
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Official Citation:Harold Pimentel, Marilyn Parra, Sherry Gee, Dana Ghanem, Xiuli An, Jie Li, Narla Mohandas, Lior Pachter, John G. Conboy; A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis. Nucleic Acids Res 2014; 42 (6): 4031-4042. doi: 10.1093/nar/gkt1388
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74722
Deposited By: George Porter
Deposited On:04 Mar 2017 00:07
Last Modified:11 Nov 2021 05:29

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