Genome-wide identification and characterization of transfer RNA-derived small RNAs in Plasmodium falciparum

Abstract

BackgroundTransfer RNA (tRNA)-derived fragments (tRFs) have been widely identified in nature, functioning in diverse biological and pathological situations. Yet, the presence of these small RNAs in Plasmodium spp. remains unknown. Systematic identification and characterization of tRFs is therefore highly needed to understand further their roles in Plasmodium parasites, particularly in the virulent Plasmodium falciparum parasite.ResultsGenome-wide small RNAs with sizes ranging from 18–30 nucleotides from P. falciparum were deep-sequenced via Illumina HiSeq 2000 technology. In-depth analysis revealed the presence of a vast number of small RNAs originating from tRNA-coding genes, responsible for 22.4% of the total reads as the second predominant group. Three P. falciparum-derived tRF types (ptRFs) were identified as 5'ptRFs, mid-ptRFs and 3'ptRFs. The majority (90%) of ptRFs were derived from tRNAs that coded eight amino acids: Pro, Phe, Asn, Gly, Cys, Gln, His and Ala. Stem-loop reverse transcription polymerase chain reaction further confirmed the presence of tRFs in the blood stages of P. falciparum. Four new motifs with an enriched G/C feature were determined at cleavage sites that might guide the generation of ptRFs.ConclusionsTo our knowledge, this is the first report of a genome-wide investigation of ptRFs from Plasmodium species. The identification of ptRFs reveals a complex small RNA system manipulated by the malaria parasite, and might promote research on the function of tRFs in the pathogenesis of Plasmodium infections.Electronic supplementary materialThe online version of this article (10.1186/s13071-019-3301-6) contains supplementary material, which is available to authorized users.

Noncoding RNAs in Apicomplexan Parasites: An Update

“…and regulate gene expression in P. falciparum in one study [67]. These findings raise the intriguing hypothesis that the parasite might utilize host Argonaute 2 for its own gene regulation [68].…”

“…Many of these unclassified RNAs are conserved among different Plasmodium species and are differentially expressed between early and late intraerythrocytic stages [69]. Additionally, a potential novel class of sncRNAs derived from tRNA fragments was revealed in P. falciparum [68]. tRNA-derived small RNAs (tsRNAs) have been reported in several protist organisms, including Tetrahymena [70], Giardia lamblia [71], Trypanosoma cruzi [72], and in Leishmania donovani exosomes [73].…”

Global Survey of miRNAs and tRNA-derived Small RNAs From Human Parasitic Protist Trichomonas Vaginalis

“…The similarity of tRFs and miRNAs also resulted in misannotation and cross-mapping of these two groups. In some species lack of miRNA molecules, such as Plasmodium parasites, tRFs might act as alternative regulators to accomplish the intense posttranscriptional regulation needed during the rapid morphological change [10]. In agellated protozoan Giardia lamblia, the abundant tRFs were involved in the differentiation process, while the previously reported miRNAs were found absent or misannotated [19].…”

“…Endonucleolytic cleavages of both mature and precursor tRNAs near the D-anticodon-or TψC-arm lead to the generation of tRFs. Despite the nomenclature to describe the types of tRFs is to be consistent, they are typically classi ed into four subclasses: 5'tRFs, 3'tRFs (or 3'CCA tRFs), 3'UtRFs (tRF-1), and internal tRFs (itRFs or mid-tRFs) in terms of their positions mapped to tRNAs [8,9,10]. tRFs are constitutively and conservatively expressed in organisms from lower archaea to mammals, however, their biological roles and mechanisms of action remain largely unclear.…”

Deciphering the Plasmodium epitranscriptome as a mechanism of translational control

“…An emerging paradigm of tRNA fragments (tRFs) that could serve as regulators has been found in other organisms [137,168]. Two papers report the presence of these cleaved tRNA molecules, but neither of the papers have been able to attribute any functionality representing an observational, nevertheless important study [151,169]. In other eukaryotes, proteins like DICER and Argonaute which form the miRNA silencing complex have been shown to interact with tRFs [168].…”