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dc.contributor.authorDumler, J.S.
dc.contributor.authorSinclair, S.H.
dc.contributor.authorShetty, A.C.
dc.date.accessioned2019-04-29T19:00:57Z
dc.date.available2019-04-29T19:00:57Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85041795904&doi=10.3389%2ffcimb.2018.00014&partnerID=40&md5=b2fa444a1103bdb330a068d2f62a4461
dc.identifier.urihttp://hdl.handle.net/10713/8894
dc.description.abstractEukaryotic proteome diversity exceeds that encoded within individual genes, and results in part from alternative splicing events of pre-messenger RNA. The diversity of these splicing events can shape the outcome in development and differentiation of normal tissues, and is important in pathogenic circumstances such as cancer and some heritable conditions. A role for alternative splicing of eukaryotic genes in response to viral and intracellular bacterial infections has only recently been recognized, and plays an important role in providing fitness for microbial survival, while potentially enhancing pathogenicity. Anaplasma phagocytophilum survives within mammalian neutrophils by reshaping transcriptional programs that govern cellular functions. We applied next generation RNAseq to ATRA-differentiated HL-60 cells established to possess transcriptional and functional responses similar to A. phagocytophilum-infected human neutrophils. This demonstrated an increase in transcripts with infection and high proportion of alternatively spliced transcript events (ASEs) for which predicted gene ontology processes were in part distinct from those identified by evaluation of single transcripts or gene-level analyses alone. The alternative isoforms are not on average shorter, and no alternative splicing in genes encoding spliceosome components is noted. Although not evident at gene-level analyses, individual spliceosome transcripts that impact nearly all spliceosome components were significantly upregulated. How the distinct GO processes predicted by ASEs are regulated by infection and whether they are relevant to fitness or pathogenicity of A. phagocytophilum should be addressed in more detailed studies. Copyright 2018 Sinclair and Shetty.en_US
dc.description.sponsorshipThe authors acknowledge the assistance technical team members at the Institute of Genome Sciences, University of Maryland, Baltimore for help with library preparation and Illumina sequencing. The experimental infections and samples were processed at the University of Maryland, Baltimore, and analysis was done in part at the Institute for Genome Sciences (AS) and Uniformed Service University of the Health Sciences (JSD). This work was funded by grant R01AI044102 from the National Institutes of Allergy and Infectious Diseases/National Institutes of Health, and in part from the University of Maryland Baltimore, Department of Pathology and the Uniformed Services University of the Health Sciences to JSDen_US
dc.description.urihttps://dx.doi.org/10.3389/fcimb.2018.00014en_US
dc.language.isoen_USen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Cellular and Infection Microbiology
dc.subjectintracellular infectionen_US
dc.subjectRNAseqen_US
dc.subject.meshAnaplasma phagocytophilumen_US
dc.subject.meshGene Ontologyen_US
dc.subject.meshRNA Isoformsen_US
dc.subject.meshSpliceosomesen_US
dc.titleAlternative splicing of differentiated myeloid cell transcripts after infection by Anaplasma phagocytophilum impacts a selective group of cellular programsen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fcimb.2018.00014
dc.identifier.pmid29456968


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