title: A dynamic intron retention program in the mammalian megakaryocyte and erythrocyte lineages.
abstract: Intron retention (IR) is a form of alternative splicing that can impact 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 to 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.
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, United States;
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Edwards
authors.affiliation: Bioinformatics Lab, Centenary Institute, Camperdown, NSW, Australia;
authors.forename: William
authors.initials: W
authors.lastname: Ritchie
authors.affiliation: Gene and Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, NSW, Austria;
authors.forename: Justin J-L
authors.initials: JJ
authors.lastname: Wong
authors.affiliation: Gene and Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, NSW, Australia;
authors.forename: Ulf
authors.initials: U
authors.lastname: Schmitz
authors.affiliation: Bioinformatics Lab, Centenary Institute, Camperdown, NSW, Australia;
authors.forename: Robert
authors.initials: R
authors.lastname: Middleton
authors.affiliation: Laboratory of Membrane Biology, New York Blood Center, New York, NY, United States;
authors.forename: Xiuli
authors.initials: X
authors.lastname: An
authors.affiliation: Red Cell Physiology Laboratory, New York Blood Center, New York, NY, United States;
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
authors.affiliation: Gene and Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, NSW, Australia;
authors.forename: John E J
authors.initials: JE
authors.lastname: Rasko
authors.affiliation: Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, United States blobel@email.chop.edu.
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Blobel