• Journal of Genetic Medicine
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• v.10 no.1
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• pp.27-32
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• 2013

Post-transcriptional nucleotide sequence modification of transcripts by RNA editing is an important molecular mechanism in the regulation of protein function and is associated with a variety of human disease phenotypes. Identification of RNA editing sites is the basic step for studying RNA editing. Databases and bioinformatics resources are used to annotate and evaluate as well as identify RNA editing sites. No method is free of limitations. Correctly establishing an analytic pipeline and strategic application of both experimental and bioinformatics methods constitute the first step in investigating RNA editing. This review summarizes modern bioinformatics approaches and related resources for RNA editing research.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5005-5006
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• 2015

Gastric cancer as one of the most common cancers worldwide has various genetic and environmental risk factors including Helicobacter pylori (H.pylori) infection. Recently, loss of a tumor suppressor gene named promyelocytic leukemia (PML) has been identified in gastric cancer. However, no mutation has been found in this gene in gastric cancer samples. Cag A H.pylori protein has been shown to exert post transcriptional regulation of some tumor suppressor genes. In order to assess such a mechanism for PML degradation, we performed in silico analyses to establish any interaction between PML and Cag A proteins. In silico interaction and docking studies showed that these two proteins may have stable interactions. In addition, we showed that imatinib kinase inhibitor can restore PML function by inhibition of casein kinase 2.

• Molecules and Cells
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• v.39 no.4
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• pp.281-285
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• 2016

Almost all of eukaryotic mRNAs are subjected to polyadenylation during mRNA processing. Recent discoveries showed that many of these mRNAs contain more than one polyadenylation sites in their 3' untranslated regions (UTR) and that alternative polyadenylation (APA) is prevalent among these genes. Many biological processes such as differentiation, proliferation, and tumorigenesis have been correlated to global APA events in the 3' UTR of mRNAs, suggesting that these APA events are tightly regulated and may play important physiological roles. In this review, recent discoveries in the physiological roles of APA events, as well as the known and proposed mechanisms are summarized. Perspective for future directions is also discussed.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.330.1-330.1
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• 2002

Arginine methylation is a common post-translation protein modification in eukaryotic cells. Protein-arginine N-methyltransferase transfer methyl groups from S-adenosyl-L-methionine to the guanidino group of arginine residues. However. The significant of this modification has been questionable. because it occurs rarely and is present at very low abundance. Recently, the discovery of two protein arginine methyltransferase, PRMT1 and CARM1, as cofactors required for responses to muclear Hormone receptors provided an indicationthat arginine methylationhave an important role in transcriptional regulation. (omitted)

• Journal of Nutrition and Health
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• v.42 no.5
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• pp.434-441
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• 2009

Ferroportin-1 (FPN) is a transporter protein that is known to mediate iron export from macrophages. The purpose of this study was to investigate the effect of copper on the regulation of FPN gene expression in J774 mouse macrophage cells. J774 cells were treated with various concentrations of $CuSO_4$ and RT-PCR analyses were performed to measure the steady-state levels of mRNAs for FPN and divalent metal transporter 1 (DMT1, an iron importer). Copper treatment significantly increased FPN mRNAs in a dose-dependent manner, but didn't change the levels of DMT1 mRNA. Experiments with transcriptional inhibitor actinomycin D (0.5 ${\mu}g$/mL) revealed that copper treatment did not affect the half-life of FPN mRNAs in J774 cells. On the other hand, results from luciferase reporter assays showed that copper directly stimulated the promoter activity of FPN. In summary, our data showed copper induced FPN mRNA of macrophages via a transcriptional rather than post-transcriptional mechanisms.

• Journal of Life Science
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• v.28 no.3
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• pp.376-387
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• 2018

Among a variety of environmental stresses heat, cold, chilling, high salt, drought, and so on exposed to plants, drought stress has been reported as a crucial factor to adversely affect the growth and productivity of plants. Therefore, to understand the mechanism for the drought stress signal transduction pathway in plants is more helpful to develop useful crops that display the enhanced tolerance against drought stress, and to expand crop growing areas. The signal transduction pathway for the drought stress in plants is largely categorized into two types; ABA-dependent pathway and ABA-independent pathway. It has been reported that two transcription factors, AREB/ABF and DREB2, play predominant roles in ABA-dependent and ABA-independent pathways, respectively. In addition to transcriptional regulation mediated by AREB/ABF and DREB2 transcription factors, post-translational modification (such as phosphorylation and ubiquitination) and epigenetic control are importantly involved in the signal transduction for drought stress. In this paper, we review current understanding of signal transduction pathway on drought stress in plants, especially focusing on the biological roles of a variety of signaling components related to drought stress response. Further understanding the mechanism of drought resistance in plants through this review will be useful to establish theoretical basis for developing drought tolerant crops in the future.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3971-3977
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• 2016

Background: Breast cancer, the commonest cancer among women in the world, ranks top in India with an incidence rate of 1,45,000 new cases and mortality rate of 70,000 women every year. Chemotherapy outcome for breast cancer is hampered due to poor response and irreversible dose-dependent cardiotoxicity which is determined by genetic variations in drug metabolizing enzymes and transporters. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, induces expression of drug metabolizing enzymes (DMEs) and transporters leading to regulation of xenobiotic metabolism. Materials and Methods: A genomic region spanning PXR 3' UTR was amplified and sequenced using genomic DNA isolated from 96 South Indian breast cancer patients. Genetic variants observed in our study subjects were queried in miRSNP to establish SNPs that alter miRNA binding sites in PXR 3' UTR. In addition, enrichment analysis was carried out to understand the network of miRNAs and PXR in drug metabolism using DIANA miRpath and miRwalk pathway prediction tools. Results: In this study, we identified SNPs rs3732359, rs3732360, rs1054190, rs1054191 and rs6438550 in the PXR 3; UTR region. The SNPs rs3732360, rs1054190 and rs1054191 were located in the binding site of miR-500a-3p, miR-532-3p and miR-374a-3p resulting in the altered PXR level due to the deregulation of post-transcriptional control and this leads to poor treatment response and toxicity. Conclusions: Genetic variants identified in PXR 3' UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for interindividual variability in treatment response and toxicity associated with chemotherapy.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.6
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• pp.876-887
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• 2015

Dicer, an ribonuclease type III type endonuclease, is the key enzyme involved in biogenesis of microRNAs (miRNAs) and small interfering RNAs (siRNAs), and thus plays a critical role in RNA interference through post transcriptional regulation of gene expression. This enzyme has not been well studied in the Indian water buffalo, an important species known for disease resistance and high milk production. In this study, the primary coding sequence (5,778 bp) of bubaline dicer (GenBank: AB969677.1) was determined and the bubaline Dicer1 biocomputationally characterized to determine the phylogenetic signature among higher eukaryotes. The evolutionary tree revealed that all the transcript variants of Dicer1 belonging to a specific species were within the same node and the sequences belonging to primates, rodents and lagomorphs, avians and reptiles formed independent clusters. The bubaline dicer1 is closely related to that of cattle and other ruminants and significantly divergent from dicer of lower species such as tapeworm, sea urchin and fruit fly. Evolutionary divergence analysis conducted using MEGA6 software indicated that dicer has undergone purifying selection over the time. Seventeen divergent sequences, representing each of the families/taxa were selected to study the specific regions of positive vis-$\grave{a}$-vis negative selection using different models like single likelihood ancestor counting, fixed effects likelihood, and random effects likelihood of Datamonkey server. Comparative analysis of the domain structure revealed that Dicer1 is conserved across mammalian species while variation both in terms of length of Dicer enzyme and presence or absence of domain is evident in the lower organisms.

• KSBB Journal
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• v.24 no.3
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• pp.217-226
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• 2009

p53 undergoes various post-translational modifications, including phosphorylation, ubiquitination, sumoylation, acetylation, methylation, and poly(ADP-ribosyl)ation. Modification of p53 widely affects to various functions of p53. Acetylation and phosphorylation of p53 have been studied for regulating its transcriptional activity which is observed in various stress condition. Otherwise, ubiquitination of p53 by Mdm2 has been well-studied as a canonical ubiquitin-mediated proteasomal degradation pathway. Moreover several investigators have recently reported that ubiquitination of p53 modulates not only its proteasome-dependent degradation by poly-ubiquitination but also its localization and transcriptional activity by mono-ubiquitination which usually does not serve the proteasome dependent degradation. Here we review recent studies on the cellular functions of p53 regulated by post-translational modifications, particularly focusing on mechanisms of ubiquitination.

• IMMUNE NETWORK
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• v.14 no.3
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• pp.138-148
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• 2014

MicroRNAs (miRNAs) are endogenous small RNA molecules best known for their function in post-transcriptional gene regulation. Immunologically, miRNA regulates the differentiation and function of immune cells and its malfunction contributes to the development of various autoimmune diseases including systemic lupus erythematosus (SLE). Over the last decade, accumulating researches provide evidence for the connection between dysregulated miRNA network and autoimmunity. Interruption of miRNA biogenesis machinery contributes to the abnormal T and B cell development and particularly a reduced suppressive function of regulatory T cells, leading to systemic autoimmune diseases. Additionally, multiple factors under autoimmune conditions interfere with miRNA generation via key miRNA processing enzymes, thus further skewing the miRNA expression profile. Indeed, several independent miRNA profiling studies reported significant differences between SLE patients and healthy controls. Despite the lack of a consistent expression pattern on individual dysregulated miRNAs in SLE among these studies, the aberrant expression of distinct groups of miRNAs causes overlapping functional outcomes including perturbed type I interferon signalling cascade, DNA hypomethylation and hyperactivation of T and B cells. The impact of specific miRNA-mediated regulation on function of major immune cells in lupus is also discussed. Although research on the clinical application of miRNAs is still immature, through an integrated approach with advances in next generation sequencing, novel tools in bioinformatics database analysis and new in vitro and in vivo models for functional evaluation, the diagnostic and therapeutic potentials of miRNAs may bring to fruition in the future.