A bioinformatic survey of RNA-binding proteins in Plasmodium

Abstract

BackgroundThe malaria parasites in the genus Plasmodium have a very complicated life cycle involving an invertebrate vector and a vertebrate host. RNA-binding proteins (RBPs) are critical factors involved in every aspect of the development of these parasites. However, very few RBPs have been functionally characterized to date in the human parasite Plasmodium falciparum.MethodsUsing different bioinformatic methods and tools we searched P. falciparum genome to list and annotate RBPs. A representative 3D models for each of the RBD domain identified in P. falciparum was created using I-TESSAR and SWISS-MODEL. Microarray and RNAseq data analysis pertaining PfRBPs was performed using MeV software. Finally, Cytoscape was used to create protein-protein interaction network for CITH-Dozi and Caf1-CCR4-Not complexes.ResultsWe report the identification of 189 putative RBP genes belonging to 13 different families in Plasmodium, which comprise 3.5 % of all annotated genes. Almost 90 % (169/189) of these genes belong to six prominent RBP classes, namely RNA recognition motifs, DEAD/H-box RNA helicases, K homology, Zinc finger, Puf and Alba gene families. Interestingly, almost all of the identified RNA-binding helicases and KH genes have cognate homologs in model species, suggesting their evolutionary conservation. Exploration of the existing P. falciparum blood-stage transcriptomes revealed that most RBPs have peak mRNA expression levels early during the intraerythrocytic development cycle, which taper off in later stages. Nearly 27 % of RBPs have elevated expression in gametocytes, while 47 and 24 % have elevated mRNA expression in ookinete and asexual stages. Comparative interactome analyses using human and Plasmodium protein-protein interaction datasets suggest extensive conservation of the PfCITH/PfDOZI and PfCaf1-CCR4-NOT complexes.ConclusionsThe Plasmodium parasites possess a large number of putative RBPs belonging to most of RBP families identified so far, suggesting the presence of extensive post-transcriptional regulation in these parasites. Taken together, in silico identification of these putative RBPs provides a foundation for future functional studies aimed at defining a unique network of post-transcriptional regulation in P. falciparum.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2092-1) contains supplementary material, which is available to authorized users.

A Plasmodium yoelii Mei2-Like RNA Binding Protein Is Essential for Completion of Liver Stage Schizogony

“…1A). A recent bioinformatics survey of RBPs in Plasmodium uncovered 72 RRM-containing proteins, 40 of which contain only one RRM domain, among them, PlasMei2, and the predicted threedimensional structure of PlasMei2 aligned with that of previously a crystalized RRM_2 domain (30). The RRM_2 domain shares amino acid conservation with RRMs of the sex lethal and HuD proteins, both of which bind single-stranded AU-rich RNA, suggesting that PlasMei2 may behave similarly (21).…”

“…PlasMei2 is highly conserved among Plasmodium species (see Fig. S1 in the supplemental material) and is the only Plasmodium protein that contains an RRM_2 domain (30). The Plasmodium RRM_2 shows a high degree of similarity to other Mei2 RRM_2 domains, based on a comparison to representative sequences from alveolates, fungi, and plants (Fig.…”

Translational regulation in blood stages of the malaria parasite Plasmodium spp.: systems‐wide studies pave the way

“…Future work could focus on specific sets of mRNAs that are subject to translational control at different stages of the parasite lifecycle as well as RBPs that exhibit features similar to P-granule components. 44…”

“…The prevalence of post-transcriptional control is also supported by the apparent lack of specialized transcription factors encoded by the parasite genome, relative to genes encoding RNAbinding and -regulatory proteins. [42][43][44] Similar to other eukaryotes, the life of a Plasmodium spp. mRNA begins in the nucleus, when the transcriptional machinery is recruited to the promoter of a gene to synthesize pre-mRNA (or nascent mRNA) that corresponds to the 5 0 -untranslated region (UTR), coding sequence (CDS), introns, and 3 0 UTR of the gene (Figure 2).…”

A putative RNA binding protein from Plasmodium vivax apicoplast

“…One of them (PVX_084415 or apiRBP in this manuscript) is a putative RNA binding protein (RBP) displaying a predicted N‐terminal signal peptide and a single RNA recognition motif (RRM). In P. falciparum , 189 genes have been annotated as putative RBPs: 179 of them possess an ortholog in P. vivax , including the one coding apiRBP . Unfortunately, most of them lack definitive functional annotations and only a few have been structurally characterized (e.g., PDB: and ).…”