Messenger RNA Surveillance: Current Understanding, Regulatory Mechanisms, and Future Implications.

Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved surveillance mechanism in eukaryotes primarily deployed to ensure RNA quality control by eliminating aberrant transcripts and also involved in modulating the expression of several physiological transcripts. NMD, the mRNA surveillance pathway, is a major form of gene regulation in eukaryotes. NMD serves as one of the most significant quality control mechanisms as it primarily scans the newly synthesized transcripts and differentiates the aberrant and non-aberrant transcripts. The synthesis of truncated proteins is restricted, which would otherwise lead to cellular dysfunctions. The up-frameshift factors (UPFs) play a central role in executing the NMD event, largely by recognizing and recruiting multiple protein factors that result in the decay of non-physiological mRNAs. NMD exhibits astounding variability in its ability across eukaryotes in an array of pathological and physiological contexts. The detailed understanding of NMD and the underlying molecular mechanisms remains blurred. This review outlines our current understanding of NMD, in regulating multifaceted cellular events during development and disease. It also attempts to identify unanswered questions that deserve further investigation.

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.

Green synthesis of Fe2O3-Ag nanocomposite using Psidium guajava leaf extract: An eco-friendly and recyclable adsorbent for remediation of Cr(VI) from aqueous media.

An environmental friendly and cost effective method was used for the preparation of silver­iron oxide (α-Fe2O3-Ag) nanocomposite using guava (Psidium guajava) leaf extract, which can be used as an adsorbent for decontamination of chromium (VI) ions from aqueous media. XRD analysis revealed that both Iron oxide and silver nanoparticles are crystalline in nature with face-centered cubic and rhombohedral geometry respectively. The FESEM micrographs of Fe2O3-Ag nanocomposite displayed irregular shaped particles with an average size of 50-90 nm. BET surface area analysis suggests that the prepared Fe2O3-Ag nanocomposites are mesoporous in nature with surface area of 122.72 m2/g. The adsorption of Cr(VI) was pH dependent and maximum adsorption occurred at pH = 4 with maximum adsorption capacity of 71.34 mg/g. Thermodynamic parameters reveals that the Cr(VI) adsorption on Fe2O3-Ag surface is endothermic and spontaneous in nature. The adsorbed Cr(VI) on Fe2O3-Ag surface was recovered and can be reused up to five cycles.

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.