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Genetics
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
DNA transcription to RNA (nucleus)Initiation, elongation, termination (Figure 2.3).Mediated by RNA polymerase.Pre-messenger RNA (mRNA) matures to form mature mRNA (see Chapter 1).
The Smallpox Story
Published in Rae-Ellen W. Kavey, Allison B. Kavey, Viral Pandemics, 2020
Rae-Ellen W. Kavey, Allison B. Kavey
Poxviruses differ from most other DNA viruses in that they replicate in the cytoplasm rather than in the nucleus of susceptible cells. To accomplish this, they have a battery of enzymes including DNA-dependent RNA polymerase which are used to transform basic building materials – amino acids, nucleotides and lipids parasitized from the infected cell – into components of the new virion. The DNA-dependent RNA polymerase transcribes messenger RNA into DNA. The virus also has an inner and outer membrane envelope; the outer envelope contains viral-specific polypeptides, including hemagglutinin, which are involved in virus attachment to host cell surface membranes. Finally, the extreme virulence of the variola virus is derived from a set of genes that reduce the multiple defense mechanisms of host organisms. A complement-regulatory protein inactivates the host complement system and prevents the host cell from engaging the immune complement cascade. The virus can also use fusion proteins to expose the host cell to extracellular material, thereby promoting degradation.43,44
Basic Cell Biology
Published in Kedar N. Prasad, Handbook of RADIOBIOLOGY, 2020
Like DNA, RNA is also a polynucleotide chain and consists of four bases, sugar, and phosphoric acid. RNA differs from DNA in the following respects: (1) it has sugar in the form of ribose rather than deoxyribose, and (2) it has pyrimidine base uracil in place of thymine. The enzyme RNA polymerase is required for RNA synthesis, and the enzyme RNAse degrades RNA. There are several classes of mammalian RNA, three of which are most important: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). All these types of RNA participate in protein biosynthesis.
Potential therapeutic targets for Mpox: the evidence to date
Published in Expert Opinion on Therapeutic Targets, 2023
Siddappa N Byrareddy, Kalicharan Sharma, Shrikesh Sachdev, Athreya S. Reddy, Arpan Acharya, Kaylee M. Klaustermeier, Christian L Lorson, Kamal Singh
The most sought-after antiviral targets for all viruses are the components of the nucleic acid replication machinery. To date, ~100 antivirals are available in the US. The majority of these drugs target Human Immunodeficiency Virus (HIV) (42), hepatitis C (18), hepatitis B (10), and herpesviruses (10). Fifteen out of 42 currently approved antiretrovirals target HIV-1 reverse transcriptase (HIV-1 RT), underlining that nucleic acid polymerase is the most important therapeutic target. In poxviruses, there are at least two nucleic acid replicating complexes: (i) a multi-subunit DNA-dependent RNA polymerase (vRNAP) complex and (ii) a multi-subunit DNA replication holoenzyme. The cryo-EM structure of the VACV vRNAP transcription complex provided the details of subunit arrangements and the mechanism of poxvirus transcription [26]. No antiviral drugs targeting vRNAP components have been approved for any poxvirus RNA transcription component.
Vaccines on demand, part II: future reality
Published in Expert Opinion on Drug Discovery, 2023
Andrew J. Geall, Zoltan Kis, Jeffrey B. Ulmer
The RNA component of both mRNA and saRNA vaccines is synthesized using a cell-free in vitro transcription reaction, which can be completed in 2 hours [1,40–42]. Thereby, the T7 RNA polymerase creates the RNA based on a template DNA. Following synthesis, the RNA is purified using one or more chromatography unit operations and usually several tangential flow ultrafiltration and diafiltration unit operations. Removal of product-related impurities (e.g. double-stranded RNA and partially degraded RNA) can be challenging, however the following chromatography techniques can be used for this: oligo(dT) affinity, reverse-phase, hydrophobic interaction, ion exchange, and multi-modal chromatography [1,21,40–42]. After downstream purification, the RNA is formulated into lipid nanoparticles (LNPs) using microfluidics equipment [43,44], impingement jet mixers [45], T-junction mixers [44], multi-inlet vortex mixers [46] or pressurized tanks [47]. The LNP-encapsulated RNA is then purified for example, by tangential flow ultrafiltration and diafiltration. Next, the RNA-LNP solution is sent for fill-finish. However, the fill-finish processes as well as the plasmid DNA production, purification, and linearization were not modeled in this study.
Molecular mechanisms of ferroptosis and their role in inflammation
Published in International Reviews of Immunology, 2023
Feng Wang, Jingya He, Ruxiao Xing, Tong Sha, Bin Sun
There is no clearly defined pathogenesis of ferroptosis; however, iron overload and the concomitantly occurring lipid peroxidation and inflammation are the three distinguishing signs of ferroptosis. The accumulation of iron caused by abnormal metabolism is considered a factor in aggravation of inflammation [18]. One of the latest discoveries pertaining to nuclear factor erythroid 2-related factor 2 (Nrf2) downstream signal transduction is the resistance to ferroptosis. Nrf2 resists ferroptosis by coordinating iron/metal metabolism, intermediate metabolism, and GSH synthesis/metabolism [19]. Nrf2 activates several downstream metabolic pathways that regulate reduction of free iron, inhibition of lipid peroxidation, and elevation in GSH. levels. Another important cellular protective mechanism of Nrf2 acts via the anti-inflammatory pathway. In addition to breaking the vicious circle of inflammation and local ROS accumulation through redox regulation, Nrf2 inhibits nuclear factor-κB (NF-κB) transcription [20]. NF-κB and Nrf2 have complex associations with each other. There are several effective NF-κB binding sites in the promoter region of Nrf2 [21]. Nrf2 and IκB kinase share an identical degradation mechanism, which is mediated by Keap1 [22]. Nrf2 and NF-κB compete for the binding site of p300 [23]. Binding to its extension region prevents the recruitment of RNA polymerase II. Nrf2 also inhibits the pro-inflammatory genes encoding IL-6 and IL-1b [24].