Evidence for regulated expression of Telomeric Repeat-containing RNAs (TERRA) in parasitic trypanosomatids

Abstract

The Telomeric Repeat-containing RNAs (TERRA) participate in the homeostasis of telomeres in higher eukaryotes. Here, we investigated the expression of TERRA in Leishmania spp. and Trypanosoma brucei and found evidences for its expression as a specific RNA class. The trypanosomatid TERRA are heterogeneous in size and partially polyadenylated. The levels of TERRA transcripts appear to be modulated through the life cycle in both trypanosomatids investigated, suggesting that TERRA play a stage-specific role in the life cycle of these early-branching eukaryotes.

Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome

“…Nonetheless, R-loop association with apparently all T. brucei centromeres appears to reveal a conserved correlation with these DNA elements, perhaps related to chromatin modification (123) or cell cycle signalling (124), despite pronounced divergence of the kinetoplastid kinetochore complex that binds centromeres (125,126). Finally, previous work in T. brucei (127) and Leishmania (94) has revealed the existence of TERRA RNA, with over expression of TbRH1 suppressing the levels of R-loops at T. brucei telomere repeats. However, the extent to which (sub)telomeric R-loops might contribute to kinetoplastid biology, such as the expression or stability of telomere-proximal genes, has been little explored.…”

“…The effects of R-loop accumulation in the VSG expression sites (ES) that are actively transcribed in BSF T. brucei are explored in detail elsewhere (Briggs et al, BioRxiv https://doi.org/10.1101/361451), while DRIP-seq patterns at the procyclin loci and metacyclic (m) VSG expression sites, both of which display gene expression repression in this life cycle stage (93), are shown in Supplementary Figure S4. Most DRIP-seq signal detected in the mVSG expression sites was downstream of the VSG genes, which are adjacent to the telomeric repeat (Supplementary Figure S4B), and may therefore be due to TERRA RNA derived from the active BSF VSG ES (94). In Tbrh1–/– cells, enriched regions were also detected upstream of the mVSG coding regions and are likely due to transcription of the normally silent mVSGs in the absence of TbRH1 (Briggs et al, BioRxiv https://doi.org/10.1101/361451).…”

Trypanosoma bruceiPolIE suppresses telomere recombination

“…The active ES-adjacent telomere is transcribed by RNA Pol I into a long non-coding telomere repeat containing RNA (TERRA) (43,46,64). Together with the telomere DNA, TERRA has a propensity to form the telomeric R-loop (65), a higher than WT level of which has been shown to induce more frequent telomere/subtelomere recombination in T. brucei (43,46).…”

Keeping Balance Between Genetic Stability and Plasticity at the Telomere and Subtelomere of Trypanosoma brucei

“…This repressive effect is position-dependent, where in general stronger effects are observed for genes located closer to the telomere, hence the name telomere position effect or telomeric silencing ( Renauld et al, 1993 ). On the other hand, at least at some chromosome ends, the telomere sequence is transcribed into a long, non-coding RNA called TElomere Repeat-containing RNA (TERRA) in a number of organisms including T. brucei ( Rudenko and Van der Ploeg, 1989 ; Damasceno et al, 2017 ; Nanavaty et al, 2017 ; Saha et al, 2019 , 2021 ), several other kinetoplastids and Plasmodium falciparum ( Rudenko and Van der Ploeg, 1989 ; Damasceno et al, 2017 ; Morea et al, 2021 ), human ( Azzalin et al, 2007 ), mouse ( Schoeftner and Blasco, 2008 ), fission ( Bah et al, 2012 ) and budding yeasts ( Luke et al, 2008 ), and birds ( Solovei et al, 1994 ). TERRA exhibits a propensity to form an R-loop structure with the telomere DNA ( Toubiana and Selig, 2018 ).…”