Plasmodium falciparum DDX17 is an RNA helicase crucial for parasite development

Abstract

Malaria is one of the major global health concerns still prevailing in this 21st century. Even the effect of artemisinin combination therapies (ACT) have declined and causing more mortality across the globe. Therefore, it is important to understand the basic biology of malaria parasite in order to find novel drug targets. Helicases play important role in nucleic acid metabolism and are components of cellular machinery in various organisms. In this manuscript we have performed the biochemical characterization of homologue of DDX17 from Plasmodium falciparum (PfDDX17). Our results show that PfDDX17 is an active RNA helicase and uses mostly ATP for its function. The qRT-PCR experiment results suggest that PfDDX17 is highly expressed in the trophozoite stage and it is localised mainly in the cytoplasm and in infected RBC (iRBC) membrane mostly in the trophozoite stage. The dsRNA knockdown study suggests that PfDDX17 is important for cell cycle progression. These studies report the biochemical functions of PfDDX17 helicase and further augment the fundamental knowledge about helicase families of P. falciparum .

Epitranscriptomics in parasitic protists: Role of RNA chemical modifications in posttranscriptional gene regulation

“…Through various proteomic assays, it was found to form a complex with XRN1 and MEIOC proteins to successfully alleviate mRNA structure adjacent to m 6 A locations [ 147 ]. In Plasmodium , PfDDX17 is an ATP-dependent RNA helicase found most abundantly in the trophozoite stage, suggesting its involvement in resolving mRNA structures for modulating protein expression in other asexual, blood stages [ 148 ].…”

“…Through various proteomic assays, it was found to form a complex with XRN1 and MEIOC proteins to successfully alleviate mRNA structure adjacent to m 6 A locations [147]. In Plasmodium, PfDDX17 is an ATP-dependent RNA helicase found most abundantly in the trophozoite stage, suggesting its involvement in resolving mRNA structures for modulating protein expression in other asexual, blood stages [148]. It remains ultimately unknown if m 6 A plays a role in resolving secondary structures in Plasmodium, Toxoplasma, and Trypanosoma; however, its enrichment has been found within the coding sequence implying its placement being intentional.…”

Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part IV. Plasmodium spp.

“…Recently, two Indian studies [42,43] were conducted on Plasmodium helicases. In the first, the investigators reported existence of two proteins crucially involved in P. falciparum mitochondrial genome repair, PfRad51, and Bloom helicase (PfBlm).…”

In-Silico Functional Annotation of Plasmodium falciparum Hypothetical Proteins to Identify Novel Drug Targets

“…With the emerging sequencing technologies, various efforts were facilitated by annotating the Plasmodium genome ( Kissinger et al, 2002 ; Bahl et al, 2003 ). Multiple studies based on proteome and genome were conducted to develop novel technologies to understand disease-resistance mechanisms in Plasmodium ( Sardar et al, 2021 ; Sourabh et al, 2021 ). While the advancement of sequencing technologies are highly beneficial to understand specific pathways and mechanism related to the disease, the most undesirable aspect for any newly sequenced genome is when almost half of the annotated proteins or genes are in the uncharacterized category and annotated as “Hypothetical proteins (HPs)” ( Galperin and Koonin, 2004 ; Singh et al, 2019 ).…”