title: A global transcriptional analysis of Plasmodium falciparum malaria reveals a novel family of telomere-associated lncRNAs.
abstract: BACKGROUND
  Mounting evidence suggests a major role for epigenetic feedback in Plasmodium falciparum transcriptional regulation. Long non-coding RNAs (lncRNAs) have recently emerged as a new paradigm in epigenetic remodeling. We therefore set out to investigate putative roles for lncRNAs in P. falciparum transcriptional regulation.
  
  
  RESULTS
  We used a high-resolution DNA tiling microarray to survey transcriptional activity across 22.6% of the P. falciparum strain 3D7 genome. We identified 872 protein-coding genes and 60 putative P. falciparum lncRNAs under developmental regulation during the parasite's pathogenic human blood stage. Further characterization of lncRNA candidates led to the discovery of an intriguing family of lncRNA telomere-associated repetitive element transcripts, termed lncRNA-TARE. We have quantified lncRNA-TARE expression at 15 distinct chromosome ends and mapped putative transcriptional start and termination sites of lncRNA-TARE loci. Remarkably, we observed coordinated and stage-specific expression of lncRNA-TARE on all chromosome ends tested, and two dominant transcripts of approximately 1.5 kb and 3.1 kb transcribed towards the telomere.
  
  
  CONCLUSIONS
  We have characterized a family of 22 telomere-associated lncRNAs in P. falciparum. Homologous lncRNA-TARE loci are coordinately expressed after parasite DNA replication, and are poised to play an important role in P. falciparum telomere maintenance, virulence gene regulation, and potentially other processes of parasite chromosome end biology. Further study of lncRNA-TARE and other promising lncRNA candidates may provide mechanistic insight into P. falciparum transcriptional regulation.
authors.affiliation: Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Broadbent
authors.forename: Daniel
authors.initials: D
authors.lastname: Park
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Wolf
authors.forename: Daria
authors.initials: D
authors.lastname: Van Tyne
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Sims
authors.forename: Ulf
authors.initials: U
authors.lastname: Ribacke
authors.forename: Sarah
authors.initials: S
authors.lastname: Volkman
authors.forename: Manoj
authors.initials: M
authors.lastname: Duraisingh
authors.forename: Dyann
authors.initials: D
authors.lastname: Wirth
authors.forename: Pardis C
authors.initials: PC
authors.lastname: Sabeti
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002875:Chromosomes; D018507:Gene Expression Regulation, Developmental; D017125:Genes, Protozoan; D056426:Genetic Loci; D018503:Genome, Protozoan; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D011544:Pseudogenes; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D016615:Telomere / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D022661:RNA, Untranslated; D014157:Transcription Factors