A global transcriptional analysis of Plasmodium falciparum malaria reveals a novel family of telomere-associated lncRNAs

Abstract

BackgroundMounting 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.ResultsWe 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.ConclusionsWe 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.

Characterization of the Unusual Bidirectional ves Promoters Driving VESA1 Expression and Associated with Antigenic Variation in Babesia bovis

“…However, noncoding RNAs (ncRNAs) are gaining recognition for playing a variety of roles in many systems, including gene silencing (43) and enhancement (40) and establishment of chromatin structure (53). Recently, ncRNAs associated with chromatin structure at telomeres have been identified in the related Apicomplexan malaria parasite Plasmodium falciparum (10). No evidence is yet available demonstrating actual mechanisms of ves gene silencing.…”

Antisense long noncoding RNAs regulate var gene activation in the malaria parasite Plasmodium falciparum

“…However, although ncRNAs were predicted to be abundant in Plasmodium (29)(30)(31)(32)(33)(34), their function remained unknown. Here, we provide evidence that antisense lncRNAs are involved in var gene activation.…”

Making a long story short: noncoding RNAs and chromosome change

“…The parasite Plasmodium falciparum, causative agent of malaria, lacks RNA interference and methylation, but does have conserved histone-modifying enzymes, a high number of RNA-binding proteins, and requires chromatin remodeling and epigenetic regulations for blood stage-specific expression and antigenic variation of virulence genes (reviewed in Broadbent et al, 2011). Recent transcriptional profiling and analysis of the parasite also revealed lncRNAs under developmental regulation during the parasite's pathogenic human blood stage, 15 of which are long telomere-associated ncRNA genes (long ncRNA telomere-associated repetitive element transcripts (lncRNA-TARE) located on 22 of 28 P. falciparum telomeres (Broadbent et al, 2011)). UpsB-type var genes are located near these lncRNA-TARE, subtelomerically, and are subject to coordinated silencing and activity as part of antigenic variation in defense against the human immune response during malaria infection (reviewed in Cui and Miao, 2010).…”