A global transcriptional analysis of Plasmodium falciparum malaria reveals a novel family of telomere-associated lncRNAs
- Equal contributors
1 Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
2 Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA
3 Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford Street, Cambridge, MA 02138, USA
4 Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, USA
5 School of Nursing and Health Sciences, Simmons College, 300 The Fenway, Boston, MA 02115, USA
6 FAS Center for Systems Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA
7 Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
8 Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA
Genome Biology 2011, 12:R56 doi:10.1186/gb-2011-12-6-r56Published: 20 June 2011
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.
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.
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.