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.

doi:10.1093/nar/gkt1388

A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis

Journal Article · Fri Jan 17 00:00:00 EST 2014 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkt1388· OSTI ID:1625522

Pimentel, Harold ^[1]; Parra, Marilyn ^[2]; Gee, Sherry ^[2]; Ghanem, Dana ^[2]; An, Xiuli ^[3]; Li, Jie ^[3]; Mohandas, Narla ^[3]; Pachter, Lior ^[4]; Conboy, John G. ^[2]

Univ. of California, Berkeley, CA (United States); DOE/OSTI
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
New York Blood Center, New York, NY (United States)
Univ. of California, Berkeley, CA (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1625522

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 6 Vol. 42; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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SUPPA2: fast, accurate, and uncertainty-aware differential splicing analysis across multiple conditions Trincado, Juan L.; Entizne, Juan C.; Hysenaj, Gerald Genome Biology, Vol. 19, Issue 1 https://doi.org/10.1186/s13059-018-1417-1	journal	March 2018
miR167 limits anther growth to potentiate anther dehiscence Zheng, Lanjie; Nagpal, Punita; Villarino, Gonzalo Development https://doi.org/10.1242/dev.174375	journal	January 2019
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The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators Llorian, Miriam; Gooding, Clare; Bellora, Nicolas Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.10731	text	January 2016
Intron retention as a component of regulated gene expression programs Jacob, Ag; Smith, Chris Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.11024	text	January 2017
Repression by RB1 characterizes genes involved in the penultimate stage of erythroid development Zhang, Ji; Loyd, Melanie R.; Randall, Mindy S. Taylor & Francis https://doi.org/10.6084/m9.figshare.1569551	text	January 2015
Repression by RB1 characterizes genes involved in the penultimate stage of erythroid development Zhang, Ji; Loyd, Melanie R.; Randall, Mindy S. Taylor & Francis https://doi.org/10.6084/m9.figshare.1569551.v4	text	January 2015

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