Preface Repetitive DNA sequences in Phyllostachys pubescens genome Transcriptional networks: dyna... more Preface Repetitive DNA sequences in Phyllostachys pubescens genome Transcriptional networks: dynamics information fluxes A new method for the identification of leucine-rich repeats by incorporating protein secondary structure prediction MicroRNA profiling involved in human tumorigenesis using Bioinformatics tools Biobanking: the bioethical dimensions Application of next-generation DNA sequencing in medical discovery Phylogenomics Transposons: the alchemists in 'junk' disguise.
RuvB, a member of AAA+ (ATPases Associated with diverse cellular Activities) superfamily of prote... more 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 recombinan...
Helicases function as key enzymes in salinity stress tolerance, and the role and function of PDH4... more 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 ra...
In the present study, the genetic mechanisms responsible for generation of antibodies recognizing... more In the present study, the genetic mechanisms responsible for generation of antibodies recognizing the dominant epitope within a synthetic peptide PS1CT3 were examined. PS1CT3 is a peptide model antigen containing residues 28–42 of the large protein of the surface antigen of hepatitis B virus as B epitope (designated PS1), and the known T-helper-cell epitope derived from the circumsporozoite protein of the malaria parasite Plasmodium falciparum (designated CT3). To characterize the repertoire generated, the immunoglobulin heavy chain variable regions from IgM and IgG monoclonal antibodies against PS1CT3 were sequenced. Although all IgG monoclonal antibodies were directed against the immunodominant epitope, the genetic elements used were diverse. Comparison of the sequence of germ line precursor IgM to a mature IgG revealed that during maturation of the primary IgM response only the heavy chain fragment of the antibody molecule underwent somatic mutation.
The cellular response to various stresses is a universal phenomenon and involves a common set of ... more 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.
There are important challenges when investigating individual post-translational modifications (PT... more 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.
Abstract Leishmania is one of the most important protozoan parasites that causes infections in hu... more Abstract Leishmania is one of the most important protozoan parasites that causes infections in humans and is responsible for three main forms of leishmaniases—visceral (also known as kala-azar and the most serious form of the disease), cutaneous (the most common), and mucocutaneous. The availability of whole genome sequence has facilitated the genome wide analysis of genes including helicases. Helicases are ubiquitously characterized by the presence of seven to nine conserved motifs and catalyze the unwinding of nucleic acid duplexes and are involved in nucleic acid metabolism. The control of leishmaniasis is becoming increasingly challenging due to the spread of resistance with antileishmanial drugs. Helicases have been targeted to control various pathogens including viruses and for cancer control also. Whole genome of Leishmania donovani is completely sequenced, but annotation of various important genes is still in progress. A bioinformatics-based approach was used to identify the homologues in L. donovani for several human helicase families such as DEAD-box, DEAH-box, DNA repair helicases, MCM, RecQ, and RuvB families. Interestingly, we also identified an UvrD helicase in L. donovani while it was absent in the human host. This detailed genome wide in silico studies of helicases identified various important helicases, which could be used as a potential target to control the replication and transmission of the Leishmania parasite.
Preface Repetitive DNA sequences in Phyllostachys pubescens genome Transcriptional networks: dyna... more Preface Repetitive DNA sequences in Phyllostachys pubescens genome Transcriptional networks: dynamics information fluxes A new method for the identification of leucine-rich repeats by incorporating protein secondary structure prediction MicroRNA profiling involved in human tumorigenesis using Bioinformatics tools Biobanking: the bioethical dimensions Application of next-generation DNA sequencing in medical discovery Phylogenomics Transposons: the alchemists in 'junk' disguise.
RuvB, a member of AAA+ (ATPases Associated with diverse cellular Activities) superfamily of prote... more 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 recombinan...
Helicases function as key enzymes in salinity stress tolerance, and the role and function of PDH4... more 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 ra...
In the present study, the genetic mechanisms responsible for generation of antibodies recognizing... more In the present study, the genetic mechanisms responsible for generation of antibodies recognizing the dominant epitope within a synthetic peptide PS1CT3 were examined. PS1CT3 is a peptide model antigen containing residues 28–42 of the large protein of the surface antigen of hepatitis B virus as B epitope (designated PS1), and the known T-helper-cell epitope derived from the circumsporozoite protein of the malaria parasite Plasmodium falciparum (designated CT3). To characterize the repertoire generated, the immunoglobulin heavy chain variable regions from IgM and IgG monoclonal antibodies against PS1CT3 were sequenced. Although all IgG monoclonal antibodies were directed against the immunodominant epitope, the genetic elements used were diverse. Comparison of the sequence of germ line precursor IgM to a mature IgG revealed that during maturation of the primary IgM response only the heavy chain fragment of the antibody molecule underwent somatic mutation.
The cellular response to various stresses is a universal phenomenon and involves a common set of ... more 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.
There are important challenges when investigating individual post-translational modifications (PT... more 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.
Abstract Leishmania is one of the most important protozoan parasites that causes infections in hu... more Abstract Leishmania is one of the most important protozoan parasites that causes infections in humans and is responsible for three main forms of leishmaniases—visceral (also known as kala-azar and the most serious form of the disease), cutaneous (the most common), and mucocutaneous. The availability of whole genome sequence has facilitated the genome wide analysis of genes including helicases. Helicases are ubiquitously characterized by the presence of seven to nine conserved motifs and catalyze the unwinding of nucleic acid duplexes and are involved in nucleic acid metabolism. The control of leishmaniasis is becoming increasingly challenging due to the spread of resistance with antileishmanial drugs. Helicases have been targeted to control various pathogens including viruses and for cancer control also. Whole genome of Leishmania donovani is completely sequenced, but annotation of various important genes is still in progress. A bioinformatics-based approach was used to identify the homologues in L. donovani for several human helicase families such as DEAD-box, DEAH-box, DNA repair helicases, MCM, RecQ, and RuvB families. Interestingly, we also identified an UvrD helicase in L. donovani while it was absent in the human host. This detailed genome wide in silico studies of helicases identified various important helicases, which could be used as a potential target to control the replication and transmission of the Leishmania parasite.
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Papers by Renu Tuteja