A dynamic intron retention program in the mammalian megakaryocyte and erythrocyte lineages

Edwards, Christopher R., Ritchie, William, Wong, Justin J-L., Schmitz, Ulf, Middleton, Robert, An, Xiuli, Mohandas, Narla, Rasko, John E.J., and Blobel, Gerd A. (2016) A dynamic intron retention program in the mammalian megakaryocyte and erythrocyte lineages. Blood, 127 (17). e24-e34.

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Intron retention (IR) is a form of alternative splicing that can affect mRNA levels through nonsense-mediated decay or by nuclear mRNA detention. A complex, dynamic IR pattern has been described in maturing mammalian granulocytes, but it is unknown whether IR occurs broadly in other hematopoietic lineages. We globally assessed IR in primary maturing mammalian erythroid and megakaryocyte (MK) lineages as well as their common progenitor cells (MEPs). Both lineages exhibit an extensive differential IR program involving hundreds of introns and genes with an overwhelming loss of IR in erythroid cells and MKs compared with MEPs. Moreover, complex IR patterns were seen throughout murine erythroid maturation. Similarly complex patterns were observed in human erythroid differentiation, but not involving the murine orthologous introns or genes. Despite the common origin of erythroid cells and MKs, and overlapping gene expression patterns, the MK IR program is entirely distinct from that of the erythroid lineage with regards to introns, genes, and affected gene ontologies. Importantly, our results suggest that IR serves to broadly regulate mRNA levels. These findings highlight the importance of this understudied form of alternative splicing in gene regulation and provide a useful resource for studies on gene expression in the MK and erythroid lineages.

Item ID: 68987
Item Type: Article (Research - C1)
ISSN: 1528-0020
Copyright Information: © 2016 by The American Society of Hematology
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC grant 1061906, NHMRC grant 1030830
Date Deposited: 28 Sep 2021 01:03
FoR Codes: 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310204 Genomics and transcriptomics @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320505 Medical biochemistry - nucleic acids @ 50%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
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