Spatiotemporally controlled active manipulation of external micro-/nanoprobes inside living cells can lead to development innovative biomedical technologies and inspire fundamental studies various biophysical phenomena. Examples include gene silencing applications, real-time mechanical mapping the intracellular environment, studying cellular response local stress, many more. Here, for first time, internalization subsequent a system helical nanomotors driven by small rotating magnetic fields...

Nanomaterials having enzyme-like activity (nanozymes) make them suitable candidates for various biomedical applications. In this study, we demonstrate the morphology-dependent enzyme mimetic of Mn3 O4 nanoparticles. It is found that nanoparticles mimic functions all three cellular antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Interestingly, nanozyme depends on factors including size, morphology, surface area, redox properties metal ions....

The SARS-CoV-2 non-structural protein 1 (Nsp1) contains an N-terminal domain and C-terminal helices connected by a short linker region. of Nsp1 (Nsp1-C-ter) from bind in the mRNA entry channel 40S ribosomal subunit blocks entry, thereby shutting down host synthesis. suppresses immune function is vital for viral replication. Hence, appears to be attractive target therapeutics. In this study, we have silico screened Food Drug Administration (FDA)-approved drugs against Nsp1-C-ter. Among top...

Article22 July 2019Open Access Source DataTransparent process Let-7a-regulated translational readthrough of mammalian AGO1 generates a microRNA pathway inhibitor Anumeha Singh Department Biochemistry, Indian Institute Science, Bengaluru, Karnataka, India Search for more papers by this author Lekha E Manjunath Pradipta Kundu Microbiology and Cell Biology, Sarthak Sahoo Arpan Das Harikumar R Suma Paul L Fox Cellular Molecular Medicine, The Lerner Research Institute, Cleveland Clinic,...

Stop codon readthrough (SCR) is the process of continuation translation beyond stop codon, generating protein isoforms with C-terminal extensions. SCR has been observed in viruses, fungi, and multicellular organisms, including mammals. However, largely unexplored plants. In this study, we have analyzed ribosome profiling datasets to identify mRNAs that exhibit Arabidopsis thaliana. Analyses density, coverage, three-nucleotide periodicity reads mRNA region downstream provided strong evidence...

Stop codon read-through (SCR) is a process of continuation translation beyond stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to longer isoform with properties different from that the canonical isoform. MTCH2, encodes mitochondrial protein regulates metabolism, was selected as potential candidate based on evolutionary conservation observed proximal region its 3′ UTR. Here, we demonstrate translational across two evolutionarily conserved,...

It is generally believed that human mature erythrocytes do not possess functional ribosomes and therefore cannot synthesize proteins. However, the absence of translation consistent with long lifespan erythrocytes. They stay viable for about 115 d in circulatory system. Here, using a highly pure preparation erythrocytes, we demonstrate presence by polysome profiling, [35S]methionine labeling, RiboPuromycylation. labeling revealed 10% observed reticulocytes. We could observe polysomes...

Naturally occurring fluorescence has been observed in multiple species ranging from bacteria to birds. In macroscopic animals such as birds, provides a visual communication signal. However, the functional significance of this phenomenon is unknown most cases. Though photoprotection attributed under ultraviolet (UV) light some organisms, it lacks direct experimental evidence. Here, we demonstrate naturally UV eutardigrade belonging genus Paramacrobiotus. Using natural variant that...

Abstract Stop codon readthrough (SCR) is the process where translation continues beyond a stop on an mRNA. Here, we describe strategy to enhance or induce SCR in transcript-selective manner using CRISPR-dCas13 system. Using specific guide RNAs, target dCas13 region downstream of canonical codons mammalian AGO1 and VEGFA mRNAs, known exhibit natural SCR. Readthrough assays reveal enhanced these mRNAs (both exogenous endogenous) caused by dCas13-gRNA complexes. This effect associated with...

ABSTRACT FEM1B is a substrate-recognition component of the CRL2 E3 ubiquitin-protein ligase. This multi-protein complex targets specific proteins for ubiquitylation, which leads to their degradation. Here, we demonstrate regulation expression by stop codon readthrough (SCR). In this process, translating ribosomes generate C-terminally extended isoform that highly unstable. A total 81 nucleotides in proximal 3′UTR constitute necessary and sufficient cis-signal SCR. Also, they encode amino...

Nonsense mutations that result in premature stop codons the HBB gene cause β-thalassemia. This disease is characterized by a reduced hemoglobin level due to lack of β-globin. Compounds induce translational readthrough across thalassemia-causing codon will have therapeutic benefits. Currently available molecules specificity, and some them show toxicity after prolonged use. In this study, we developed an oligonucleotide-based approach codon. Oligonucleotides target mRNA downstream could...

Termination codon readthrough (TCR) is a process in which ribosomes continue to translate an mRNA beyond stop generating C-terminally extended protein isoform. Here, we demonstrate TCR mammalian <i>NNAT</i> mRNA, encodes NNAT, proteolipid important for neuronal differentiation. This programmed event driven by <i>cis</i>-acting RNA sequences present immediately upstream and downstream of the canonical negatively regulated NONO, RNA-binding known promote Unlike isoform determined that product...

ABSTRACT Several methods are available to study the regulation of gene expression at cellular and molecular levels. Adaptation these in vivo is cumbersome often requires animal sacrifice. Here, we report an assay (IVISc-L, In Vivo Imaging Subcutaneous Luminescence) . This involves subcutaneous injection a plasmid DNA encoding firefly luciferase, whose under regulatory mechanism be investigated. We could infer its regulated by detecting luminescence using imaging system. Using this assay,...

ABSTRACT A stop codon ensures termination of translation at a specific position on an mRNA. Sometimes, fails as machinery recognizes sense codon. This leads to readthrough (SCR) resulting in the continuation beyond codon, generating protein isoforms with C-terminal extension. SCR has been observed viruses, fungi, and multicellular organisms including mammals. However, is largely unexplored plants. In this study, we have analyzed ribosome profiling datasets identify mRNAs that undergo...

Abstract Stop codon readthrough (SCR) is the process where translation continues beyond a stop on an mRNA. Here, we describe strategy to enhance or induce SCR in transcript-selective manner using CRISPR-dCas13 system. Using specific guide RNAs, targeted dCas13 downstream region of canonical codons mammalian AGO1 and VEGFA, which are known exhibit natural SCR. Results assays revealed enhancement these mRNAs (both exogenous endogenous) caused by dCas13. This effect was associated with...

Abstract Naturally occurring fluorescence has been observed in multiple species ranging from bacteria to birds. In macroscopic animals such as birds and fishes, provides a visual communication signal. However, the functional significance of this phenomenon is not known most cases. Though photoprotection attributed under ultraviolet (UV) light some organisms, it lacks direct experimental evidence. Here, we have identified new eutardigrade belonging genus Paramacrobiotus , which exhibits UV...