OsRuvBL1a DNA helicase boost salinity and drought tolerance in transgenic indica rice raised by in planta transformation.

RuvBL, is a member of SF6 superfamily of helicases and is conserved among the various model systems. Recently, rice (Oryza sativa L.) homolog of RuvBL has been biochemically characterized for its ATPase and DNA helicase activities; however its involvement in stress has not been studied so far. Present investigation reports the detailed functional characterization of OsRuvBL under abiotic stresses through genetic engineering. An efficient Agrobacterium-mediated in planta transformation protocol was developed in indica rice to generate the transgenic lines and study was focused on optimization of factors to achieve maximum transformation efficiency. Overexpressing OsRuvBL1a transgenic lines showed enhanced tolerance under in vivo salinity stress as compared to WT plants. The physiological and biochemical analysis of the OsRuvBL1a transgenic lines showed better performance under salinity and drought stresses. Several stress responsive interacting partners of OsRuvBL1a were identified using Y2H system revealed to its role in stress tolerance. Functional mechanism for boosting stress tolerance by OsRuvBL1a has been proposed in this study. This integration of OsRuvBL1a gene in rice genome using in planta transformation method helped to achieve the abiotic stress resilient smart crop. This study is the first direct evidence to show the novel function of RuvBL in boosting abiotic stress tolerance in plants.

Marker-Free Rice (Oryza sativa L. cv. IR 64) Overexpressing PDH45 Gene Confers Salinity Tolerance by Maintaining Photosynthesis and Antioxidant Machinery.

Helicases function as key enzymes in salinity stress tolerance, and the role and function of PDH45 (pea DNA helicase 45) in stress tolerance have been reported in different crops with selectable markers, raising public and regulatory concerns. In the present study, we developed five lines of marker-free PDH45-overexpressing transgenic lines of rice (Oryza sativa L. cv. IR64). The overexpression of PDH45 driven by CaMV35S promoter in transgenic rice conferred high salinity (200 mM NaCl) tolerance in the T1 generation. Molecular attributes such as PCR, RT-PCR, and Southern and Western blot analyses confirmed stable integration and expression of the PDH45 gene in the PDH45-overexpressing lines. We observed higher endogenous levels of sugars (glucose and fructose) and hormones (GA, zeatin, and IAA) in the transgenic lines in comparison to control plants (empty vector (VC) and wild type (WT)) under salt treatments. Furthermore, photosynthetic characteristics such as net photosynthetic rate (Pn), stomatal conductance (gs), intercellular CO2 (Ci), and chlorophyll (Chl) content were significantly higher in transgenic lines under salinity stress as compared to control plants. However, the maximum primary photochemical efficiency of PSII, as an estimated from variable to maximum chlorophyll a fluorescence (Fv/Fm), was identical in the transgenics to that in the control plants. The activities of antioxidant enzymes, such as catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), and guaiacol peroxidase (GPX), were significantly higher in transgenic lines in comparison to control plants, which helped in keeping the oxidative stress burden (MDA and H2O2) lesser on transgenic lines, thus protecting the growth and photosynthetic efficiency of the plants. Overall, the present research reports the development of marker-free PDH45-overexpressing transgenic lines for salt tolerance that can potentially avoid public and biosafety concerns and facilitate the commercialization of genetically engineered crop plants.

Immunomodulatory Potential of Non-Classical HLA-G in Infections including COVID-19 and Parasitic Diseases.

Human Leukocyte Antigen-G (HLA-G), a polymorphic non-classical HLA (HLA-Ib) with immune-regulatory properties in cancers and infectious diseases, presents both membrane-bound and soluble (sHLA-G) isoforms. Polymorphism has implications in host responses to pathogen infections and in pathogenesis. Differential expression patterns of HLA-G/sHLA-G or its polymorphism seem to be related to different pathological conditions, potentially acting as a disease progression biomarker. Pathogen antigens might be involved in the regulation of both membrane-bound and sHLA-G levels and impact immune responses during co-infections. The upregulation of HLA-G in viral and bacterial infections induce tolerance to infection. Recently, sHLA-G was found useful to identify the prognosis of Coronavirus disease 2019 (COVID-19) among patients and it was observed that the high levels of sHLA-G are associated with worse prognosis. The use of pathogens, such as Plasmodium falciparum, as immune modulators for other infections could be extended for the modulation of membrane-bound HLA-G in COVID-19-infected tissues. Overall, such information might open new avenues concerning the effect of some pathogens such as parasites in decreasing the expression level of HLA-G to restrict pathogenesis in some infections or to influence the immune responses after vaccination among others.

Plasmodium falciparum DDX3X is a nucleocytoplasmic protein and requires N-terminal for DNA helicase activity.

Malaria is a haemato-protozoan disease which causes thousands of deaths every year. Due to the alarming increase of drug resistant strains of P. falciparum, malaria is now becoming more deadly. Helicases are the most important components of the cellular machinery without which cells are unable to survive. The importance of helicases has been proven in variety of organisms. In this study we have reported detailed biochemical characterization of human homologue of DDX3X from Plasmodium falciparum (PfDDX3X). Our study revealed that PfDDX3X is ATP- dependent DNA helicase whereas in human host it is ATP-dependent RNA helicase. We show that N-terminal is essential for its activity and it is present in nucleus and cytoplasm in intraerythrocytic developmental stages of P. falciparum 3D7 strain. Also, it is highly expressed in the schizont stage of P. falciparum 3D7strain. The present study suggests that a protein can perform different functions in different systems. The present study will help to understand the basic biology of malaria parasite P. falciparum.

The main post-translational modifications and related regulatory pathways in the malaria parasite Plasmodium falciparum: An update.

There are important challenges when investigating individual post-translational modifications (PTMs) or protein interaction network and delineating if PTMs or their changes and cross-talks are involved during infection, disease initiation or as a result of disease progression. Proteomics and in silico approaches now offer the possibility to complement each other to further understand the regulatory involvement of these modifications in parasites and infection biology. Accordingly, the current review highlights key expressed or altered proteins and PTMs are invisible switches that turn on and off the function of most of the proteins. PTMs include phosphorylation, glycosylation, ubiquitylation, palmitoylation, myristoylation, prenylation, acetylation, methylation, and epigenetic PTMs in P. falciparum which have been recently identified. But also other low-abundant or overlooked PTMs that might be important for the parasite's survival, infectivity, antigenicity, immunomodulation and pathogenesis. We here emphasize the PTMs as regulatory pathways playing major roles in the biology, pathogenicity, metabolic pathways, survival, host-parasite interactions and the life cycle of P. falciparum. Further validations and functional characterizations of such proteins might confirm the discovery of therapeutic targets and might most likely provide valuable data for the treatment of P. falciparum, the main cause of severe malaria in human.

Plasmodium falciparum DDX17 is an RNA helicase crucial for parasite development.

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.

Plasmodium falciparum DDX55 is a nucleocytoplasmic protein and a 3'-5' direction-specific DNA helicase.

Malaria is one of the major causes of mortality as well as morbidity in many tropical and subtropical countries around the world. Although artemisinin combination therapies (ACTs) are contributing to substantial decline in the worldwide malaria burden, it is becoming vulnerable by the emergence of artemisinin resistance in Plasmodium falciparum leading to clinical failure of ACTs in Southeast Asia. Helicases play important role in nucleic acid metabolic processes and have been also identified as therapeutic drug target for different diseases. Previously, it has been reported that P. falciparum contains a group of DEAD-box family of helicases which are homologous to Has1 family of yeast. Here, we present the characterization of a member of Has1 family (PlasmoDB number PF3D7_1419100) named as PfDDX55. The biochemical characterization of PfDDX55C revealed that it contains both DNA- and RNA-dependent ATPase activity. PfDDX55C unwinds partially duplex DNA in 3' to 5' direction and utilizes mainly ATP or dATP for its activity. The immunofluorescence assay and q-RT PCR analysis show that PfDDX55 is a nucleocytoplasmic protein expressed in all the intraerythrocytic development of P. falciparum 3D7 strain with maximum expression level in trophozoite stage. The LC-MS/MS experiment results and STRING analysis show that PfDDX55 interacts with AAA-ATPase which has been shown to be involved in ribosomal biogenesis.

Plasmodium falciparum DDX31 is DNA helicase localized in nucleolus.

Malaria is a major infectious disease and is responsible for millions of infections every year. As drug resistance strains of Plasmodium species are emerging, there is an urgent need to understand the parasite biology and identify new drug targets. Helicases are very important enzymes that participate in various nucleic acid metabolic processes. Previously we have reported several putative DEAD box helicases in the genome of Plasmodium falciparum 3D7 strain. In this study, we present biochemical characterization of one of the members of Has1 (Helicase associated with SET1) family of DEAD box proteins from P. falciparum 3D7 strain. PfDDX31 is a homologue of human DDX31 helicase and contains all the conserved characteristics motifs. The core PfDDX31C exhibits DNA and RNA dependent ATPase activity and unwinds partially duplex DNA by utilizing ATP or dATP only. The immunofluorescence assay results show that PfDDX31 is expressed throughout all the intraerythrocytic developmental stages in P. falciparum 3D7 strain. The co-localization with nucleolar marker PfNop1 further suggests that PfDDX31 is mostly present in nucleolus, a discrete nuclear compartment.

Cyanide produced with ethylene by ACS and its incomplete detoxification by ß-CAS in mango inflorescence leads to malformation.

Malformation of mango inflorescences (MMI) disease causes severe economic losses worldwide. Present research investigates the underlying causes of MMI. Results revealed significantly higher levels of cyanide, a by-product of ethylene biosynthesis, in malformed inflorescences (MI) of mango cultivars. There was a significant rise in ACS transcripts, ACS enzyme activity and cyanide and ethylene levels in MI as compared to healthy inflorescences (HI). Significant differences in levels of methionine, phosphate, S-adenosyl-L-methionine, S-adenosyl-L-homocysteine, ascorbate and glutathione, and activities of dehydroascorbate reductase and glutathione reductase were seen in MI over HI. Further, a lower expression of ß-cyanoalanine synthase (ß-CAS) transcript was associated with decreased cellular ß-CAS activity in MI, indicating accumulation of unmetabolized cyanide. TEM studies showed increased gum-resinosis and necrotic cell organelles, which might be attributed to unmetabolized cyanide. In field trials, increased malformed-necrotic-inflorescence (MNI) by spraying ethrel and decreased MNI by treating with ethylene inhibitors (silver and cobalt ions) further confirmed the involvement of cyanide in MMI. Implying a role for cyanide in MMI at the physiological and molecular level, this study will contribute to better understanding of the etiology of mango inflorescence malformation, and also help manipulate mango varieties genetically for resistance to malformation.

Biochemical characterization of Plasmodium falciparum parasite specific helicase 1 (PfPSH1).

Malaria, a disease caused by infection with parasites of the genus Plasmodium, causes millions of deaths worldwide annually. Of the five Plasmodium species that can infect humans, Plasmodium falciparum causes the most serious parasitic infection. The emergence of drug resistance and the ineffectiveness of old therapeutic regimes against malaria mean there is an urgent need to better understand the basic biology of the malaria parasite. Previously, we have reported the presence of parasite-specific helicases identified through genome-wide analysis of the P. falciparum (3D7) strain. Helicases are involved in various biological pathways in addition to nucleic acid metabolism, making them an important target of study. Here, we report the detailed biochemical characterization of P. falciparum parasite-specific helicase 1 (PfPSH1) and the effect of phosphorylation on its biochemical activities. The C-terminal of PfPSH1 (PfPSH1C) containing all conserved domains was used for biochemical characterization. PfPSH1C exhibits DNA- or ribonucleic acid (RNA)-stimulated ATPase activity, and it can unwind DNA and RNA duplex substrates. It shows bipolar directionality because it can translocate in both (3'-5' and 5'-3') directions. PfPSH1 is mainly localized to the cytoplasm during early stages (including ring and trophozoite stages of intraerythrocytic development), but at late stages, it is partially located in the cytoplasm. The biochemical activities of PfPSH1 are upregulated after phosphorylation with PKC. The detailed biochemical characterization of PfPSH1 will help us understand its functional role in the parasite and pave the way for future studies.

Plasmodium falciparum specific helicase 2 is a dual, bipolar helicase and is crucial for parasite growth.

Human malaria infection is a major challenge across the globe and is responsible for millions of deaths annually. Rapidly emerging drug resistant strains against the new class of anti-malarial drugs are major threat to control the disease burden worldwide. Helicases are present in every organism and have important role in various nucleic acid metabolic processes. Previously we have reported the presence of three parasite specific helicases (PSH) in Plasmodium falciparum 3D7 strain. Here we present the detailed biochemical characterization of PfPSH2. PfPSH2 is DNA and RNA stimulated ATPase and is able to unwind partially duplex DNA and RNA substrates. It can translocate in both 3' to 5' and 5' to 3' directions. PfPSH2 is expressed in all the stages of intraerythrocytic development and it is localized in cytoplasm in P. falciparum 3D7 strain. The dsRNA mediated inhibition study suggests that PfPSH2 is important for the growth and survival of the parasite. This study presents the detailed characterization of PfPSH2 and lays the foundation for future development of PfPSH2 as drug target.

Stress-induced Oryza sativa RuvBL1a is DNA-independent ATPase and unwinds DNA duplex in 3' to 5' direction.

RuvB, a member of AAA+ (ATPases Associated with diverse cellular Activities) superfamily of proteins, is essential, highly conserved and multifunctional in nature as it is involved in DNA damage repair, mitotic assembly, switching of histone variants and assembly of telomerase core complex. RuvB family is widely studied in various systems such as Escherichia coli, yeast, human, Drosophila, Plasmodium falciparum and mouse, but not well studied in plants. We have studied the transcript level of rice homologue of RuvB gene (OsRuvBL1a) under various abiotic stress conditions, and the results suggest that it is upregulated under salinity, cold and heat stress. Therefore, the OsRuvBL1a protein was characterized using in silico and biochemical approaches. In silico study confirmed the presence of all the four characteristic motifs of AAA+ superfamily-Walker A, Walker B, Sensor I and Sensor II. Structurally, OsRuvBL1a is similar to RuvB1 from Chaetomium thermophilum. The purified recombinant OsRuvBL1a protein shows unique DNA-independent ATPase activity. Using site-directed mutagenesis, the importance of two conserved motifs (Walker B and Sensor I) in ATPase activity has been also reported with mutants D302N and N332H. The OsRuvBL1a protein unwinds the duplex DNA in the 3' to 5' direction. The presence of unique DNA-independent ATPase and DNA unwinding activities of OsRuvBL1a protein and upregulation of its transcript under abiotic stress conditions suggest its involvement in multiple cellular pathways. The first detailed characterization of plant RuvBL1a in this study may provide important contribution in exploiting the role of RuvB for developing the stress tolerant plants of agricultural importance.

Plasmodium falciparum specific helicase 3 is nucleocytoplasmic protein and unwinds DNA duplex in 3' to 5' direction.

Plasmodium falciparum is responsible for most dangerous and prevalent form of malaria. The emergence of multi drug resistant parasite hindered the prevention of malaria burden worldwide. Helicases are omnipresent enzymes, which play important role in nucleic acid metabolism and can be used as potential targets for development of novel therapeutics. The genome wide analysis of P. falciparum 3D7 strain revealed some novel parasite specific helicases, which are not present in human host. Here we report the detailed biochemical characterization of P. falciparum parasite specific helicase 3 (PfPSH3). The characteristic ATPase and helicase activities of PfPSH3 reside in its N-terminal region (PfPSH3N) as it contains all the conserved signature motifs whereas the C-terminal does not show any detectable biochemical activity. PfPSH3N also shows DNA helicase activity in the 3'-5' direction. The immunofluorescence microscopy results show that PSH3 is localized in nucleus as well as in cytoplasm during different stages such as trophozoite and early schizont stages of intraerythrocytic development. This report sets the foundation for further study of parasite specific helicases and will be helpful in understanding the parasite biology.

Introduction to the Special Issue on Malaria.

This minireview series highlights recent developments in malaria research. The reviews cover diverse topics, from conventional antimalarial therapies and the strategies used to circumvent the emergence of drug resistance, to the latest approaches for the discovery and validation of new druggable targets and for the development of effective antimalarial vaccines.

Unraveling the importance of the malaria parasite helicases.

Malaria is a human parasitic disease caused by infection from Plasmodium species, particularly Plasmodium falciparum. Each year millions of people are infected with malaria and large numbers of deaths result due to this deadly infection. P. falciparum contains 14 chromosomes, nearly 5400 genes and a multistage life cycle in humans and mosquitoes. The control of malaria is still a challenge as the parasite is continuously developing resistance to available antimalarial drugs and the mosquito vector is developing resistance to insecticides. The availability of P. falciparum genome has resulted in the identification of parasite-specific proteins that can be targeted without harmful effects to the human host. Toward this goal, we have been working on the identification and characterization of helicases in order to find parasite-specific helicases, which can be used as novel drug targets to tackle the rising problem of drug resistance. Helicases are ATP-dependent nucleic acid unwinding enzymes. The P. falciparum genome analysis depicts that it contains some parasite-specific helicases and homologs to most of the human helicases. Here, we present an overview of P. falciparum helicases and their importance in parasite growth and survival.

Simultaneous Expression of PDH45 with EPSPS Gene Improves Salinity and Herbicide Tolerance in Transgenic Tobacco Plants.

To cope with the problem of salinity- and weed-induced crop losses, a multi-stress tolerant trait is need of the hour but a combinatorial view of such traits is not yet explored. The overexpression of PDH45 (pea DNA helicase 45) and EPSPS (5-enoylpruvyl shikimate-3-phosphate synthase) genes have been reported to impart salinity and herbicide tolerance. Further, the understanding of mechanism and pathways utilized by PDH45 and EPSPS for salinity and herbicide tolerance will help to improve the crops of economical importance. In the present study, we have performed a comparative analysis of salinity and herbicide tolerance to check the biochemical parameters and antioxidant status of tobacco transgenic plants. Collectively, the results showed that PDH45 overexpressing transgenic lines display efficient tolerance to salinity stress, while PDH45+EPSPS transgenics showed tolerance to both the salinity and herbicide as compared to the control [wild type (WT) and vector control (VC)] plants. The activities of the components of enzymatic antioxidant machinery were observed to be higher in the transgenic plants indicating the presence of an efficient antioxidant defense system which helps to cope with the stress-induced oxidative-damages. Photosynthetic parameters also showed significant increase in PDH45 and PDH45+EPSPS overexpressing transgenic plants in comparison to WT, VC and EPSPS transgenic plants under salinity stress. Furthermore, PDH45 and PDH45+EPSPS synergistically modulate the jasmonic acid and salicylic acid mediated signaling pathways for combating salinity stress. The findings of our study suggest that pyramiding of the PDH45 gene with EPSPS gene renders host plants tolerant to salinity and herbicide by enhancing the antioxidant machinery thus photosynthesis.

Genome Wide In silico Analysis of the Mismatch Repair Components of Plasmodium falciparum and Their Comparison with Human Host.

Malaria a major parasitic infection globally particularly in tropical and sub-tropical regions of the world is responsible for about 198 million cases and estimated deaths due to this disease are about 0.6 million. The emergence of drug resistance in the malaria parasite is alarming and it is necessary to understand its underlying cause and molecular mechanisms. It has been established that drug resistant malaria parasites have defective mismatch repair (MMR) therefore it is essential to study this pathway and its components in detail. Recently a number of non-synonymous Single Nucleotide Polymorphisms have been reported in genes involved in MMR pathways. PfMLH is an endonuclease essential to restore the MMR in drug resistant strains of Plasmodium falciparum. Considering all these facts about the role of MMR in emergence of drug resistant parasite, in this manuscript we report a genome wide analysis of the components of the MMR pathway such as MLH, Pms1, MSH2-1, MSH2-2, MSH6, and UvrD using in silico bioinformatics based approaches. The phylogenetic analysis revealed evolutionary closeness with the MMR components of various organisms. It is noteworthy that P. falciparum contains two homologs of MSH2, which are located on different chromosomes. The structural modeling of these components showed their similarity with the human/yeast MMR components. The docking studies reveal that PfUvrD and PfMLH interact with each other. The in silico identification of interacting partners of the major MMR components identified numerous P. falciparum specific proteins. In line with our previous studies the present study will also contribute significantly to understand the MMR pathway of malaria parasite.

ATPase activity of Plasmodium falciparum MLH is inhibited by DNA-interacting ligands and dsRNAs of MLH along with UvrD curtail malaria parasite growth.

Malaria caused by Plasmodium falciparum is the major disease burden all over the world. Recently, the situation has deteriorated because the malarial parasites are becoming progressively more resistant to numerous commonly used antimalarial drugs. Thus, there is a critical requirement to find other means to restrict and eliminate malaria. The mismatch repair (MMR) machinery of parasite is quite unique in several ways, and it can be exploited for finding new drug targets. MutL homolog (MLH) is one of the major components of MMR machinery, and along with UvrD, it helps in unwinding the DNA. We have screened several DNA-interacting ligands for their effect on intrinsic ATPase activity of PfMLH protein. This screening suggested that several ligands such as daunorubicin, etoposide, ethidium bromide, netropsin, and nogalamycin are inhibitors of the ATPase activity of PfMLH, and their apparent IC50 values range from 2.1 to 9.35 µM. In the presence of nogalamycin and netropsin, the effect was significant because in their presence, the V max value dropped from 1.024 µM of hydrolyzed ATP/min to 0.596 and 0.643 µM of hydrolyzed ATP/min, respectively. The effect of double-stranded RNAs of PfMLH and PfUvrD on growth of P. falciparum 3D7 strain was studied. The parasite growth was significantly inhibited suggesting that these components belonging to MMR pathway are crucial for the survival of the parasite.

Function of heterotrimeric G-protein γ subunit RGG1 in providing salinity stress tolerance in rice by elevating detoxification of ROS.

MAIN CONCLUSION: The present study provides evidence of a unique function of RGG1 in providing salinity stress tolerance in transgenic rice without affecting yield. It also provides a good example for signal transduction from the external environment to inside for enhanced agricultural production that withstands the extreme climatic conditions and ensures food security. The role of heterotrimeric G-proteins functioning as signalling molecules has not been studied as extensively in plants as in animals. Recently, their importance in plant stress signalling has been emerging. In this study, the function of rice G-protein γ subunit (RGG1) in the promotion of salinity tolerance in rice (Oryza sativa L. cv. IR64) was investigated. The overexpression of RGG1 driven by the CaMV35S promoter in transgenic rice conferred high salinity tolerance even in the presence of 200 mM NaCl. Transcript levels of antioxidative genes, i.e., CAT, APX, and GR, and their enzyme activities increased in salinity-stressed transgenic rice plants suggesting a better antioxidant system to cope the oxidative-damages caused by salinity stress. The RGG1-induced signalling events that conferred tolerance to salinity was mediated by increased gene expression of the enzymes that scavenged reactive oxygen species. In salinity-stressed RGG1 transgenic lines, the transcript levels of RGG2, RGB, RGA, DEP1, and GS3 also increased in addition to RGG1. These observations suggest that most likely the stoichiometry of the G-protein complex was not disturbed under stress. Agronomic parameters, endogenous sugar content (glucose and fructose) and hormones (GA3, zeatin and IAA) were also higher in the transgenic plants compared with the wild-type plants. A BiFC assay confirmed the interaction of RGG1 with different stress-responsive proteins which play active roles in signalling and prevention of aggregation of proteins under stress-induced perturbation. The present study will help in understanding the G-protein-mediated stress tolerance in plants.

Emerging functions of helicases in regulation of stress survival in malaria parasite Plasmodium falciparum and their comparison with human host.

The cellular response to various stresses is a universal phenomenon and involves a common set of stress responses that are largely independent of the type of stress. The response to stress is complex and cells can activate multiple signaling pathways that act in concert to influence cell fate and results in a specific cellular outcome, including reduction in macromolecular synthesis by shared pathways, cell cycle arrest, DNA repair, senescence and/or apoptosis. Whether cells mount a protective response or die depends to a great degree on the nature and duration of the stress and the particular cell type. Helicases play essential roles in DNA replication, repair, recombination, transcription and translation, and also participate in RNA metabolic processes including pre-mRNA processing, ribosome biogenesis, RNA turnover, export, translation, surveillance, storage and decay. In order to survive in the human host, the malaria parasite Plasmodium falciparum has to handle variety of stresses, which it encounters during the erythrocytic stages of its life cycle. In recent past the role of helicases in imparting various stress responses has emerged. Therefore in the present review an attempt has been made to highlight the emerging importance of helicases in stress responses in malaria parasite and their comparison with human host is also presented. It is noteworthy that PfDHX33 and PfDDX60 are larger in size and different in sequence as compared to the HsDHX33 and HsDDX60. The study suggests that helicases are multifunctional and play major role in helping the cells to combat various stresses.