title: Transcriptomic profiling of gene expression and RNA processing during Leishmania major differentiation.
abstract: Protozoan parasites of the genus Leishmania are the etiological agents of leishmaniasis, a group of diseases with a worldwide incidence of 0.9-1.6 million cases per year. We used RNA-seq to conduct a high-resolution transcriptomic analysis of the global changes in gene expression and RNA processing events that occur as L. major transforms from non-infective procyclic promastigotes to infective metacyclic promastigotes. Careful statistical analysis across multiple biological replicates and the removal of batch effects provided a high quality framework for comprehensively analyzing differential gene expression and transcriptome remodeling in this pathogen as it acquires its infectivity. We also identified precise 5' and 3' UTR boundaries for a majority of Leishmania genes and detected widespread alternative trans-splicing and polyadenylation. An investigation of possible correlations between stage-specific preferential trans-splicing or polyadenylation sites and differentially expressed genes revealed a lack of systematic association, establishing that differences in expression levels cannot be attributed to stage-regulated alternative RNA processing. Our findings build on and improve existing expression datasets and provide a substantially more detailed view of L. major biology that will inform the field and potentially provide a stronger basis for drug discovery and vaccine development efforts.
authors.affiliation: Department of Cell Biology and Molecular Genetics, 3128 Bioscience Research Building, University of Maryland, College Park, MD 20742, USA Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA.
authors.forename: Laura A L
authors.initials: LA
authors.lastname: Dillon
authors.affiliation: Department of Mathematics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Kwame
authors.initials: K
authors.lastname: Okrah
authors.affiliation: Department of Cell Biology and Molecular Genetics, 3128 Bioscience Research Building, University of Maryland, College Park, MD 20742, USA Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA.
authors.forename: V Keith
authors.initials: VK
authors.lastname: Hughitt
authors.affiliation: Department of Cell Biology and Molecular Genetics, 3128 Bioscience Research Building, University of Maryland, College Park, MD 20742, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Suresh
authors.affiliation: Department of Cell Biology and Molecular Genetics, 3128 Bioscience Research Building, University of Maryland, College Park, MD 20742, USA Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cell Biology and Molecular Genetics, 3128 Bioscience Research Building, University of Maryland, College Park, MD 20742, USA Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Fernandes
authors.affiliation: Department of Cell Biology and Molecular Genetics, 3128 Bioscience Research Building, University of Maryland, College Park, MD 20742, USA Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA.
authors.forename: A Trey
authors.initials: AT
authors.lastname: Belew
authors.affiliation: Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA Department of Computer Science, University of Maryland, College Park, MD 20742, USA.
authors.forename: Hector
authors.initials: H
authors.lastname: Corrada Bravo
authors.affiliation: Department of Cell Biology and Molecular Genetics, 3128 Bioscience Research Building, University of Maryland, College Park, MD 20742, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Mosser
authors.affiliation: Department of Cell Biology and Molecular Genetics, 3128 Bioscience Research Building, University of Maryland, College Park, MD 20742, USA Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA elsayed@umd.edu.
authors.forename: Najib M
authors.initials: NM
authors.lastname: El-Sayed
mesh_terms: D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D063990:Gene Ontology; D017125:Genes, Protozoan; D018320:Leishmania major / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D026723:Polyadenylation; D012323:RNA Processing, Post-Transcriptional; D017423:Sequence Analysis, RNA; D020040:Trans-Splicing