Nonsense-Mediated mRNA Decay: Mechanistic Insights and Physiological Significance.

Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved surveillance mechanism across eukaryotes and also regulates the expression of physiological transcripts, thus involved in gene regulation. It essentially ensures recognition and removal of aberrant transcripts. Therefore, the NMD protects the cellular system by restricting the synthesis of truncated proteins, potentially by eliminating the faulty mRNAs. NMD is an evolutionarily conserved surveillance mechanism across eukaryotes and also regulates the expression of physiological transcripts, thus involved in gene regulation as well. Primarily, the NMD machinery scans and differentiates the aberrant and non-aberrant transcripts. A myriad of cellular dysfunctions arise due to production of truncated proteins, so the NMD core proteins, the up-frameshift factors (UPFs) recognizes the faulty mRNAs and further recruits factors resulting in the mRNA degradation. NMD exhibits astounding variability in its ability in regulating cellular mechanisms including both pathological and physiological events. But, the detailed underlying molecular mechanisms in NMD remains blurred and require extensive investigation to gain insights on cellular homeostasis. The complexity in understanding of NMD pathway arises due to the involvement of numerous proteins, molecular interactions and their functioning in different steps of this process. Moreover methods such as alternative splicing generates numerous isoforms of mRNA, so it makes difficulties in understanding the impact of alternative splicing on the efficiency of NMD functioning. Role of NMD in cancer development is very complex. Studies have shown that in some cases cancer cells use NMD pathway as a tool to exploit the NMD mechanism to maintain tumor microenvironment. A greater level of understanding about the intricate mechanism of how tumor used NMD pathway for their benefits, a strategy can be developed for targeting and inhibiting NMD factors involved in pro-tumor activity. There are very little amount of information available about the NMD pathway, how it discriminate mRNAs that are targeted by NMD from those that are not. This review highlights our current understanding of NMD, specifically the regulatory mechanisms and attempts to outline less explored questions that warrant further investigations. Taken as a whole, a detailed molecular understanding of the NMD mechanism could lead to wide-ranging applications for improving cellular homeostasis and paving out strategies in combating pathological disorders leaping forward toward achieving United Nations sustainable development goals (SDG 3: Good health and well-being).

Microbased biorefinery for gold nanoparticle production: recent advancements, applications and future aspects.

Multifaceted utility of nanomaterials is indispensable to meet the environmental challenges across the globe. Nanomaterials substantially contribute in delineating the rapidly advancing field of nanotechnology. Recently, primary emphasis has been laid down on augmenting the biological methodologies for the synthesis of nanomaterials. In this aspect, green nanotechnology has revolutionized the entire process of nanosynthesis. Essentially biofabrication of nanoparticles have long-range applications, primarily in the field of medical applications such as drug delivery, cancer diagnostics and genetic engineering processes. Biocompatible and stable nanoparticles synthesized from biological source can be an effective approach against the chemically synthesized owing to their non-expensive and eco-friendly attributes. Biological systems including bacteria, yeasts, fungi and plants have already been exploited in the field of nanotechnology. Use of fungi seems to be a very effective and economical approach for the synthesis of gold nanoparticles. Gold nanoparticles possess anti-oxidation activity, are highly stable and biocompatible in nature. Fungi-mediated nanoparticle biosynthesis is more advantageous as compared to bacterial synthesis. Fungi secrete large amounts of enzymes, whereas the enzyme secretion of yeasts is weak. Here, we have reported the recent advancements and future implications in the field of gold nanoparticle production and applications.

Pathogen-Associated Molecular Pattern-Triggered Immunity Involves Proteolytic Degradation of Core Nonsense-Mediated mRNA Decay Factors During the Early Defense Response.

Nonsense-mediated mRNA decay (NMD), an mRNA quality control process, is thought to function in plant immunity. A subset of fully spliced (FS) transcripts of Arabidopsis (Arabidopsis thaliana) resistance (R) genes are upregulated during bacterial infection. Here, we report that 81.2% and 65.1% of FS natural TIR-NBS-LRR (TNL) and CC-NBS-LRR transcripts, respectively, retain characteristics of NMD regulation, as their transcript levels could be controlled posttranscriptionally. Both bacterial infection and the perception of bacteria by pattern recognition receptors initiated the destruction of core NMD factors UP-FRAMESHIFT1 (UPF1), UPF2, and UPF3 in Arabidopsis within 30 min of inoculation via the independent ubiquitination of UPF1 and UPF3 and their degradation via the 26S proteasome pathway. The induction of UPF1 and UPF3 ubiquitination was delayed in mitogen-activated protein kinase3 (mpk3) and mpk6, but not in salicylic acid-signaling mutants, during the early immune response. Finally, previously uncharacterized TNL-type R transcripts accumulated in upf mutants and conferred disease resistance to infection with a virulent Pseudomonas strain in plants. Our findings demonstrate that NMD is one of the main regulatory processes through which PRRs fine-tune R transcript levels to reduce fitness costs and achieve effective immunity.

Over-expression of a rice tau class glutathione s-transferase gene improves tolerance to salinity and oxidative stresses in Arabidopsis.

Glutathione S-transferases (GSTs) are multifunctional proteins encoded by large gene family in plants, which play important role in cellular detoxification of several endobiotic and xenobiotic compounds. Previously, we suggested the diverse roles of rice GST gene family members in plant development and various stress responses based on their differential expression. In this study, we report the functional characterization of a rice tau class GST gene, OsGSTU4. OsGSTU4 fusion protein was found to be localized in nucleus and cytoplasm. The over-expression of OsGSTU4 in E. coli resulted in better growth and higher GST activity under various stress conditions. Further, we raised over-expression transgenic Arabidopsis plants to reveal its in planta function. These transgenic lines showed reduced sensitivity towards plant hormones, auxin and abscisic acid. Various analyses revealed improved tolerance in transgenic Arabidopsis plants towards salinity and oxidative stresses, which may be attributed to the lower accumulation of reactive oxygen species and enhanced GST activity. In addition, microarray analysis revealed up-regulation of several genes involved in stress responses and cellular detoxification processes in the transgenic plants as compared to wild-type. These results suggest that OsGSTU4 can be used as a good candidate for the generation of stress-tolerant crop plants.

Validation of internal control genes for quantitative gene expression studies in chickpea (Cicer arietinum L.).

The real-time polymerase chain reaction (PCR) data requires normalization with an internal control gene expressed at constant levels under all the experimental conditions being analyzed for accurate and reliable gene expression results. In this study, the expression of 12 candidate internal control genes, including ACT1, EF1alpha, GAPDH, IF4a, TUB6, UBC, UBQ5, UBQ10, 18SrRNA, 25SrRNA, GRX and HSP90, in a diverse set of 18 tissue samples representing different organs/developmental stages and stress conditions in chickpea (Cicer arietinum L.) has been validated. Their expression levels vary considerably in various tissue samples analyzed. The expression levels of EF1alpha and HSP90 are most constant across various organs/developmental stages analyzed. Similarly, the expression levels of IF4a and GAPDH are most constant across various stress conditions. A set of two most stable genes is found sufficient for accurate and reliable normalization of real-time PCR data in the given set of tissue samples of chickpea. The genes with most constant expression identified in this study should be useful for normalization of gene expression data in a wide variety of tissue samples in chickpea.