Extracellular vesicles produced by the protozoan parasite Trichomonas vaginalis contain a preferential cargo of tRNA-derived small RNAs

Artuyants, Anastasiia; Campos, Túlio de Lima; Anand, K.; Johnson, Patricia J.; Dauros-Singorenko, Priscila; Phillips, Anthony R.J.; Simões-Barbosa, Augusto

doi:10.1016/j.ijpara.2020.07.003

Cited by 34 publications

(33 citation statements)

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“…tRNA-halves are generally believed to be the products of tRNAs under nutritional, biological or physicochemical stresses [2,4,36], while T. vaginalis parasites were cultured regularly at low density in our experiment. The presence of tRNA-halves was also noted in a recent study in which nine tRNA-halves were discovered from extracellular vesicles of the parasite T. vaginalis cultured under conditions of no external stress [7]. It is notable that no extra iron was included in both studies.…”

Section: Discussionmentioning

confidence: 53%

“…However, the misinterpretation of miRNAs discovered using the same methods in a closely related parasite, G. lamblia [19], hint at an ambiguous fate of Trichomonas miRNA molecules. Albeit a recent study revealed the occurrence of nine tRNA-halves in extracellular vesicles from T. vaginalis [7], their global expression profile in this parasite still remains to be revealed. It is therefore necessary to revisit the small RNAs in T. vaginalis, in particular tsR-NAs and miRNAs, using advanced high-throughput deep sequencing to achieve a better understanding of the snR-NAs in this parasite.…”

Section: Introductionmentioning

confidence: 98%

“…The conventional tRNA-halves are produced by a single ribonucleolytic cleavage within the anticodon loops of mature tRNAs under stress conditions, and thus they have also been referred to as tRNA-derived stress-induced small RNAs (tiRNAs) [2][3][4][5][6]. However, a recent study presented evidence of tRNA-halves being expressed in a non-stress condition [7], suggesting that the factors affecting the genesis of tRNA-halves might need to be re-evaluated. Endonucleolytic cleavages of both mature and precursor tRNAs near the D-,anticodon-,or TψC-arm lead to the generation of tRFs.…”

Section: Introductionmentioning

confidence: 99%

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Global survey of miRNAs and tRNA-derived small RNAs from the human parasitic protist Trichomonas vaginalis

et al. 2021

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Background Small non-coding RNAs play critical regulatory roles in post-transcription. However, their characteristics in Trichomonas vaginalis, the causative agent of human sexually transmitted trichomoniasis, still remain to be determined. Methods Small RNA transcriptomes from Trichomonas trophozoites were deep sequenced using the Illumina NextSeq 500 system and comprehensively analyzed to identify Trichomonas microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs). The tsRNA candidates were confirmed by stem-loop quantitative reverse transcription-PCR, and motifs to guide the cleavage of tsRNAs were predicted using the GLAM2 algorithm. Results The miRNAs were found to be present in T. vaginalis but at an extremely low abundance (0.0046%). Three categories of endogenous Trichomonas tsRNAs were identified, namely 5′tritsRNAs, mid-tritsRNAs and 3′tritsRNAs, with the 5′tritsRNAs constituting the dominant category (67.63%) of tsRNAs. Interestingly, the cleavage site analysis verified both conventional classes of tRNA-derived fragments (tRFs) and tRNA-halves in tritsRNAs, indicating the expression of tRNA-halves in the non-stress condition. A total of 25 tritsRNAs were experimentally confirmed, accounting for 78.1% of all tested candidates. Three motifs were predicted to guide the production of tritsRNAs. The results prove the expression of tRFs and tRNA-halves in the T. vaginalis transcriptome. Conclusions This is the first report of genome-wide investigation of small RNAs, particularly tsRNAs and miRNAs, from Trichomonas parasites. Our findings demonstrate the expression profile of tsRNAs in T. vaginalis, while miRNA was barely detected. These results may promote further research aimed at gaining a better understanding of the evolution of small non-coding RNA in T. vaginalis and their functions in the pathogenesis of trichomoniasis.

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Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Global survey of miRNAs and tRNA-derived small RNAs from the human parasitic protist Trichomonas vaginalis

et al. 2021

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“…Although tRNA fragments are only a small fraction of sRNAs in OMVs, their predominance in host cells suggests that tRNA fragments may have longer half-lives than other more abundant sRNAs. Moreover, EVs produced by Trichomonas vaginalis encapsulate abundant 5' tRNA halves and fuse with benign prostate hyperplasia (BPH-1) cells to deliver sRNAs (Artuyants et al, 2020). In addition, EVs secreted by Gram-positive bacteria, fungi, and even intracellular parasites also deliver protein toxins and sRNA products to host cells to modulate the host immune response (Rodrigues et al, 2008;Rivera et al, 2010;Silverman et al, 2010;Resch et al, 2016;Munhoz da Rocha et al, 2020).…”

Section: Extracellular Vesicles Are Important Mediators Of Intercellular Communication and Delivery Of Trna Fragments To The Hostmentioning

confidence: 99%

Transfer RNA-Derived Fragments, the Underappreciated Regulatory Small RNAs in Microbial Pathogenesis

2021

Front. Microbiol.

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In eukaryotic organisms, transfer RNA (tRNA)-derived fragments have diverse biological functions. Considering the conserved sequences of tRNAs, it is not surprising that endogenous tRNA fragments in bacteria also play important regulatory roles. Recent studies have shown that microbes secrete extracellular vesicles (EVs) containing tRNA fragments and that the EVs deliver tRNA fragments to eukaryotic hosts where they regulate gene expression. Here, we review the literature describing microbial tRNA fragment biogenesis and how the fragments secreted in microbial EVs suppress the host immune response, thereby facilitating chronic infection. Also, we discuss knowledge gaps and research challenges for understanding the pathogenic roles of microbial tRNA fragments in regulating the host response to infection.

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“…The RNA cargo of extracellular vesicles secreted by Trichomonas vaginalis was very well characterized and found to contain predominantly 5' tRNA halves. Moreover, the RNA content was seen to be internalized by the human host cells by lipidraft mediated endocytosis, suggesting that tRNA half carried by parasitic EVs could be a possible mode of extracellular gene-modulation (52). Similarly, in both old and new world Leishmania, tRFs are highly enriched in EVs and point to a conserved packaging of tRFs in EVs (53).…”

Section: Discussionmentioning

confidence: 99%

Stress response inEntamoeba histolyticais associated with robust processing of tRNA to tRNA-halves

Sharma

Zhang

Ehrenkaufer

et al. 2021

Preprint

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tRNA-derived fragments have been reported in many different organisms and have diverse cellular roles such as regulating gene expression, inhibiting protein translation, silencing transposable elements and modulating cell proliferation. In particular tRNA halves, a class of tRNA fragments produced by the cleavage of tRNAs in the anti-codon loop, have been widely reported to accumulate under stress and regulate translation in cells. Here we report the presence of tRNA-derived fragments in Entamoeba with tRNA halves being the most abundant. We further established that tRNA halves accumulate in the parasites upon different stress stimuli such as oxidative stress, heat shock, and serum starvation. We also observed differential expression of tRNA halves during developmental changes of trophozoite to cyst conversion with various tRNA halves accumulating during early encystation. In contrast to other systems, the stress response does not appear to be mediated by a few specific tRNA halves as multiple tRNAs appear to be processed during the various stresses. Furthermore, we identified some tRNA-derived fragments are associated with Entamoeba Argonaute proteins, EhAgo2-2, and EhAgo2-3, which have a preference for different tRNA-derived fragment species. Finally, we show that tRNA halves are packaged inside extracellular vesicles secreted by amoeba. The ubiquitous presence of tRNA-derived fragments, their association with the Argonaute proteins, and the accumulation of tRNA halves during multiple different stresses including encystation suggest a nuanced level of gene expression regulation mediated by different tRNA-derived fragments in Entamoeba.

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Extracellular vesicles produced by the protozoan parasite Trichomonas vaginalis contain a preferential cargo of tRNA-derived small RNAs

Cited by 34 publications

References 42 publications

Global survey of miRNAs and tRNA-derived small RNAs from the human parasitic protist Trichomonas vaginalis

Global survey of miRNAs and tRNA-derived small RNAs from the human parasitic protist Trichomonas vaginalis

Transfer RNA-Derived Fragments, the Underappreciated Regulatory Small RNAs in Microbial Pathogenesis

Stress response inEntamoeba histolyticais associated with robust processing of tRNA to tRNA-halves

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