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Alternative splicing of arsenic (III oxidation state) methyltransferase
Published in Yong-Guan Zhu, Huaming Guo, Prosun Bhattacharya, Jochen Bundschuh, Arslan Ahmad, Ravi Naidu, Environmental Arsenic in a Changing World, 2019
Alternative splicing generates more than two mRNAs by alteration in the location and combination at the splicing sites, resulting in variant isoforms of the protein translated from a single gene. Environmental chemicals that are known to cause oxidative stress, such as paraquat and arsenic, were shown to impair control over mRNA splicing, resulting in the deregulation of the survival of motor neurons (SMN) and the induction of DNA damage in gene 45α (GADD45α). It has been reported that hydrogen peroxide (H2O2) stimulates alternative splicing of hypoxanthine guanine phosphoribosyl transferase (HPRT) and soluble guanylyl cyclase (sGC). Thus, it is apparent that oxidative stress causes splicing abnormalities on specific mRNAs. However, it remains unknown whether the control of splicing of AS3MT mRNA is vulnerable to oxidative stress.
Cell Physiology
Published in Wei-Shou Hu, Cell Culture Bioprocess Engineering, 2020
An enzyme may also be subject to allosteric regulation, meaning that its activity is modulated by the binding of an effector molecule to the enzyme. For example, the binding of the product of the reaction can decrease the enzyme activity (i.e., feedback inhibition). In many biosynthetic pathways in microbial systems, the first enzyme in the pathway is feedback inhibited by the product of the pathway. Upon the accumulation of the product, its activity is decreased to reduce the flux through the pathway and to prevent wasteful accumulation of the product. Different isozymes may be subject to different allosteric regulations. Isoforms may also respond differently to hormonal or signaling stimuli.
Genetic and Epigenetic Considerations in iPSC Technology
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Splicing is one of the mRNA processes done to exclude introns and connect exons from nascent pre-mRNA. Alternative splicing (AS) is a crucial regulation for producing multiple isoforms from a single gene by joining different sets of exons. Innovation of high-throughput sequencing and high-resolution microarray allows the genome-wide screening of unique splicing patterns in hESCs and mESCs (161–164). Recent studies identified several ESC-specific AS events and these transcriptional isoforms promote iPSC generation. Here, we highlight the functions and the importance of recently identified ESC-specific splicing variants (Table 3.1).
Bioprocessing of recombinant proteins from Escherichia coli inclusion bodies: insights from structure-function relationship for novel applications
Published in Preparative Biochemistry & Biotechnology, 2023
Kajal Kachhawaha, Santanu Singh, Khyati Joshi, Priyanka Nain, Sumit K. Singh
The refolded output generally would be a cocktail of correctly folded, misfolded, truncated, and aggregated forms of target protein.[28] It is of utmost necessity to separate the correctly folded form of the protein from the other conformational impurities for the development of a safe and efficacious biotherapeutic. While the truncated and aggregated form of the protein could easily be removed using size exclusion chromatography (SEC),[131] it is not an attractive option at the industrial scale. The SEC is characterized by small loading (usually <5% of the column volume) and operation under slow flow rates (∼50 cm/h), which exorbitantly adds to the overall cost and time of bioprocessing.[132] The biggest challenge, however, is the separation of the misfolded forms from the correctly folded proteins due to nearly the same Physio-chemical properties. The currently used approaches to separate protein isoforms include multi-modal chromatography, which uses two orthogonal dimensions of separation based on the intrinsic properties of the proteins.[133] The excellent separation efficiency offered by multi-modal chromatography is often marred by difficulties in optimizing the separation conditions and issues with the method’s reproducibility.[134]
Effects of emerging persistent organic pollutant perfluorooctane sulfonate (PFOS) on the Crustacean Gammarus insensibilis
Published in Human and Ecological Risk Assessment: An International Journal, 2019
Samir Touaylia, Abdelhafidh Khazri, Ali Mezni, Mustapha Bejaoui
Cells use antioxidant strategies and consume a lot of energy to control their level of reactive oxygen species. Antioxidant compounds such as vitamins (E, C, and Q), or carotenoids brought by food, act by trapping radicals and capturing the single electron, transforming them into stable molecules or ions (Kinsky 1989). The other strategy is enzymatic, aimed at destroying superoxides and peroxides. Thus, superoxide dismutases are capable of removing the superoxide anion by a disproportionation reaction, forming with two superoxides an oxygen molecule and a molecule of hydrogen peroxide. They exist under several isoforms forming a hydrophobic well at the center of the protein in which the superoxide anion slips. The reactional mechanism is catalyzed by a metal located in the core of the enzyme (Zelko et al.2002).
Development of capability for genome-scale CRISPR-Cas9 knockout screens in New Zealand
Published in Journal of the Royal Society of New Zealand, 2018
Francis W. Hunter, Peter Tsai, Purvi M. Kakadia, Stefan K. Bohlander, Cristin G. Print, William R. Wilson
There are, of course, caveats. CRISPR as a forward genetics tool is applicable only to phenotypes that are cell-autonomous, and thus identifiable in large populations of single, independent cells. The current sgRNA libraries do not necessarily mutate all isoforms from each gene. This is one of several reasons for considering the use of Cas9 libraries that inhibit gene expression, in parallel with knockout libraries (Rosenbluh et al. 2017). True saturation mutagenesis that includes non-coding RNA genes and intergenic regions is currently only possible for small regions of the genome. In addition, many technical challenges are being defined as the technology matures (Aguirre et al. 2016), including control of Cas nuclease-mediated toxicity and off-target mutagenesis (Morgens et al. 2017).