Transcriptomic profiling of gene expression and RNA processing during Leishmania major differentiation

Nucleic Acids Res. 2015 Aug 18;43(14):6799-813. doi: 10.1093/nar/gkv656. Epub 2015 Jul 6.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Ontology
  • Genes, Protozoan
  • Leishmania major / genetics*
  • Leishmania major / growth & development
  • Leishmania major / metabolism
  • Polyadenylation
  • RNA Processing, Post-Transcriptional*
  • Sequence Analysis, RNA
  • Trans-Splicing