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AI and Immunology Considerations in Pandemics and SARS-CoV-2 COVID-19
Published in Louis J. Catania, AI for Immunology, 2021
One of the weapons in our cells’ is an RNA surveillance mechanism called nonsense-mediated mRNA decay (NMD) that protects us from further genetic mutations that could cause disease. With the progression of new viral strains, mRNA can be easily genetically reprogrammed to recognize mutant viral strains and allows for the development of second generation vaccines that directly target processes critical to a virus’s life cycle.61
Branched chain keto acid dehydrogenase kinase (BCKDK) deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Mutations reported to date in the gene on chromosome 16 have included the null mutation R174G and a missense mutation p.L389P [2]. A C to T change in exon 4 led to a premature stop at position 156 [1], prior to the kinase domain. A single-base deletion c.G222 del in exon 2 led to a frameshift that terminated the protein at position 74 of R412 amino acids [1]. A missense mutation G671C led to a change from a highly conserved arginine at 224 to a proline. Levels of mRNA were shown to be reduced in two families studied [1], suggesting nonsense mediated decay, and enzyme protein was undetectable by western blot [1]. Mice with deficiency of BCKDK have increased basal activity of the BCKDH complex [3]. These mice developed neurologic abnormalities including seizures; histology of the brain was normal.
Non-VLPs
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Using the PP7-based approach, Hoek et al. (2019) developed an assay to visualize nonsense-mediated decay of individual mRNA molecules in real time. This made it possible to uncover real-time dynamics of NMD and revealed key mechanisms that influence the efficiency of the nonsense-mediated decay.
Transcriptomic analysis of the Non-Obstructive Azoospermia (NOA) to address gene expression regulation in human testis
Published in Systems Biology in Reproductive Medicine, 2023
Govindkumar Balagannavar, Kavyashree Basavaraju, Akhilesh Kumar Bajpai, Sravanthi Davuluri, Shruthi Kannan, Vasan S. Srini, Darshan S. Chandrashekar, Neelima Chitturi, Kshitish K. Acharya
A higher number of down-regulated genes, vs. the up-regulated ones, was expected as most spermatogenic cells would be absent or reduced in number, or non-functional or sub-optimally functional, and several key genes expressed during spermatogenesis would also be dormant or under-expressed in the testis of NOA patients. On the other hand, genes expressed in somatic cells and pre-meiotic germ cells within the testis would be proportionately enriched, and the corresponding functions would seem promoted in NOA. Genes up-regulated in NOA had an over-representation of translation, general metabolism, steroidogenesis and androgen biosynthesis, lysosome activity, extracellular matrix, and cell-adhesion-related functions. The mechanism of nonsense-mediated decay, independent of or enhanced by the role of many such RNA processing events, indicated to be important in NOA among up- or down-regulated genes, needs to be explored more. Exon Junction Complex was an interesting pathway striking among the up-regulated genes.
Genetic Study of Hereditary Angioedema Type I and Type II (First Report from Iranian Patients: Describing Three New Mutations)
Published in Immunological Investigations, 2022
Susan Nabilou, Fatemeh Pak, Zahra Alizadeh, Mohammad Reza Fazlollahi, Masoud Houshmand, Maryam Ayazi, Iraj Mohammadzadeh, Mohammad Hasan Bemanian, Abbas Fayezi, Mohammad Nabavi, Shiva Saghafi, Sajedeh Mohammadian, Parviz Kokhaei, Mostafa Moin, Zahra Pourpak
Furthermore, p.G217Vfs* (in P13) as a new frameshift mutation is located on upstream of RCL (R466-W467), leading to truncated protein. Additionally, four other reported frameshifts found in this study including p.S422Lfs*9, p.V454Gfs*18 in exon 8, p.S36Ffs*21 in exon 3, and p.L243Cfsx*9 in exon 5 failed to cover the RCL region. Moreover, p.R494* in exon 8, as a nonsense mutation within a hot spot mutated CpG dinucleotide, is responsible for early termination of mRNA translation and creating premature stop codon leading to rapid protein degradation (Amrani et al. 2006; Verpy et al. 1995). Early nonsense or frameshift mutations lead to premature stop codon and truncation protein, which result in synthesizing defective protein and generating transitory transcription via nonsense mediated mRNA decay (NMD) (Amrani et al. 2006).
Novel DNAH17 mutations associated with fertilization failures after ICSI
Published in Gynecological Endocrinology, 2021
Miaomiao Jia, Rong Shi, Xia Xue
The variant c.1048C > T was located in the N-terminal stem domain of DNAH family of genes. This variant introduces a premature stop codon in position 350, which is predicted to result in a truncated and nonfunctional protein (p.Arg350*) that lacks all six ATPase domains (AAA1, AAA2, AAA3, AAA4, AAA5 and AAA6) and a microtubule binding region (Stalk). This variant may also prevent protein production by causing mRNA degradation through nonsense-mediated decay. The variant c.3390G > A was also located in the stem domain of DNAH family of genes and is absent in the East Asian population of ExAC, gnomAD, and 1000 Genomes Project. Sequence alignment indicated that the amino acids affected by the mutation sites (p.Met1130) in human DNAH17 were highly conserved in other species, suggesting that these sites play important roles in protein function (Figure 1(D)).