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Genetics and exercise: an introduction
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Claude Bouchard, Henning Wackerhage
According to the Genome Reference Consortium, we have 20,465 genes in our human genome. Most genes start with an ATG start codon (which is transcribed into AUG in RNA) that encodes methionine as the first amino acid of a protein. Genes also end with a stop codon which can be TAG, TGA or TAA in DNA or UAG, UGA and UAA when transcribed into RNA. Three DNA bases, termed a triplet, encode one amino acid within a protein. Since there are 64 possible combinations of 4 DNA bases in a 3-base code and only 20 common amino acids to specify, the genetic code is redundant, with most amino acids being encoded by more than one triplet. Table 3.2 lists the codons encoding each amino acid.
Cancer Biology and Genetics for Non-Biologists
Published in Trevor F. Cox, Medical Statistics for Cancer Studies, 2022
the triples in brackets are codons that together will code for a particular protein. The AUG is a start codon for starting the translation, the GUG, codes for an amino acid called valine, CGC for arginine, …., CCC for proline, AAU for asparagine and UAA is a stop codon. Table 2.1 shows the 64 possible codons and their amino acids. Transfer RNA (tRNA) brings in the amino acids to match the mRNA codon coding. The chain of amino acids is a polypeptide, which is then folded into a three-dimensional structure, which is the protein. Cells do not make proteins all the time, only when they are signalled to do so.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In eukaryotic organisms, pre-mRNA is transcribed in the nucleus. Introns are then spliced out, and the mature mRNA exported from the nucleus to the cytoplasm. The small subunit of the ribosome usually starts by binding to one end of the mRNA and is joined there by various other eukaryotic initiation factors, thus forming the initiation complex. The initiation complex scans along the mRNA strand until it reaches a start codon, and then the large subunit of the ribosome attaches to the small subunit and translation of a protein begins. Backbone-modified oligomers (Figure 5.95) can bind to the RNA and block this process. Structures of peptide nucleic acids (PNAs), Morpholino Oligonucleotides and the ribose sugar modifications of locked nucleic acids (LNAs) in comparison to DNA.
Effectiveness of mRNA, protein subunit vaccine and viral vectors vaccines against SARS-CoV-2 in people over 18 years old: a systematic review
Published in Expert Review of Vaccines, 2023
Cristian Sandoval, Daniela Guerrero, Joham Muñoz, Karina Godoy, Vanessa Souza-Mello, Jorge Farías
mRNA platforms include mRNA-1273, BNT162b1, and BNT162b2. The mRNA-1273 vaccine is a lipid nanoparticle encapsulated mRNA vaccine that encodes the S-2P antigen glycoprotein, which is the S2 component, with two consecutive proline changes at amino acid positions 986 and 987 [13–15]. By using several significantly altered mRNA sequences, BNT162b1 and BNT162b2 produce long-lasting and abundant target protein expression. Both approaches use different sequences around the start codon, such as GCCACCAUG rather than GCCRCCAUGG. R and G residues at the 4th and 10th positions, respectively, are removed to improve translational initiation at a downstream AUG start codon. Following the start codon, the mRNA in BNT162b1 and BNT162b2 have a tiny flanking area with secondary structure, but the mRNA-1273 has a significantly more obvious secondary structure [16].
Discovery of RNA-targeted small molecules through the merging of experimental and computational technologies
Published in Expert Opinion on Drug Discovery, 2023
Once the number of candidate target RNA motifs is pared down to the most promising, one can assess individual motifs more thoroughly. The location of the motif on an mRNA or pre-mRNA provides clues to its function. In general, stable motifs on the 5’ untranslated region (UTR) may regulate translation [74–79], those on the junctions between the exons and introns may be involved splicing [80–82], and those on the 3’ UTR may control degradation and stabilization processes [83–86]. From a survey of the complete genomes of 340 species, Gu et al. [87] posited that stable RNA motifs near the start codon regulate translation by interfering with start codon recognition. It was also reported that highly stable motifs on the coding region may stall the ribosome and activate the ribosome-associated protein pathway, which targets newly synthesized proteins for proteasomal degradation [88]. As a rule of thumb, we select stable RNA motifs on the 5’ UTR and the coding region of the mRNA and splicing relevant RNA motifs on exon-intron junctions of the pre-mRNA as targets of small-molecule drug discovery. It is also worth considering motifs on the 3’ UTR and non-coding RNAs after verifying their therapeutic implications with experimental and computational approaches. In addition, we select RNA motifs that bind proteins, which are components of cellular metabolism or regulatory networks, as suggested by Warner et al. [17].
An update on VEXAS syndrome
Published in Expert Review of Clinical Immunology, 2023
Research from Ferrada et al. involving a retrospective case series from USA and UK has uncovered a relationship between the different mutations affecting Methionine-41 and the role of residual UBA1b in determining clinical presentation and severity of the resulting disease [11]. Methionine is coded for by the DNA nucleotide sequence ATG, the universal start codon in all eukaryotes. Though ATG (AUG once transcribed) almost exclusively fulfills this role, previous research has shown that other nucleotide sequences can act as alternative, but less efficient, start codons [12]. The most effective of these across six studies and assays include CTG, GTG, TTG and ACG [12]. Of note, although there are nine possible substitution mutations of ATG, the only Methionine-41 substitutions discovered which cause VEXAS have been from ATG (methionine) to ACG (threonine), GTG (valine) and CTG (leucine). These have all been shown to be capable of initiating some degree of translation.