A central role for Plasmodiumfalciparum subtelomeric regions in spatial positioning and telomere length regulation

Abstract

In the protozoan malaria parasite, Plasmodium falciparum, the telomere-associated sequences (TASs) of the 14 linear chromosomes display a similar higher order organization and form clusters of four to seven telomeres localized at the nuclear periphery. Experimental evidence has shown that the physical tethering of chromosome ends enhances the ectopic recombination between gene families involved in antigenic variation and parasite sequestration. Using FISH analysis, we observed that chromosome ends lacking the subtelomeric region are usually delocalized from telomere clusters, but still remain at the nuclear periphery. This indicates that subtelomeric DNA is necessary for cluster formation but is not essential for peripheral positioning. Intriguingly, these truncated chromosomes have unusually long telomeric tracts (up to three times longer than average length), showing that TASs play a role in telomere length regulation. On these chromosomes, the newly formed telomere frequently extends from truncated genes leading, in some cases, to the transcription of telomeric DNA. The implications of both subtelomeric gene expression and nuclear architecture in the virulence of this serious human pathogen are discussed.

The transcription machinery and the molecular toolbox to control gene expression in Toxoplasma gondii and other protozoan parasites

“…Some var genes are also present further upstream at the telomere-associated sequence (TAS) together with other gene families involved in antigenic variation, including the rifin genes (for a review see) [29]. Telomeres were shown to cluster at the nuclear periphery [30] and this arrangement appears to enable frequent ectopic recombination, which gives rise to a new var gene and therefore increases the repertoire of antigenic variants [31]. Expression of var genes is mutually exclusive, due to a cooperative silencing mechanism, which is controlled by two cis-acting elements.…”

Antigenic variation inPlasmodium falciparumis associated with movement ofvarloci between subnuclear locations

“…We previously identified homologues of several yeast telomere silencing factors in the P. falciparum genome (11) and have recently shown that one of these silencing factors, PfSir2, interacts with inactive subtelomeric var genes but not with active var genes (12). Other published experiments demonstrate relaxed transcription from subtelomeric loci after deletions of the subtelomeric repeat structures, indicating a role for these elements in the silencing process (13,14). However, almost nothing is known about how internal var genes are silenced.…”

Telomere as an Important Player in Regulation of Microbial Pathogen Virulence

“…5A) (Scherf et al 2001): The telomere-proximal domain consists of six Telomere-Associated Repetitive Elements (TAREs), which are variable tandem repeats (De Bruin et al 1994;Figueiredo et al 2002;Pizzi & Frontali 2001), and a couple of these elements are transcribed as long non-coding RNA (Broadbent et al 2011). The telomeredistal domain consists of a number of gene families including rif and var genes that encode virulence factors expressed at the surface of the infected host cells and involved in antigenic variation (see below) (Cheng et al 1998;Rubio et al 1996).…”