PseudoUridine & Pathways
PseudoUridine was the first modified ribonucleotide discovered 70 years ago. It is an isomer of the nucleoside uridine, in which uracil is linked by a carbon-carbon rather than a nitrogen-carbon glycosidic bond. (In this configuration, uracil is sometimes referred to as "pseudoUridine".) PseudoUridine can base pair with adenosine like uridine, but pseudouridine can alter RNA structure by improving base pairing, base stacking and backbone stability. In 2005, Katalin Karikó et al. found that the introduction of pseudoUridine into RNA reduced its immunogenicity and that the immunogenicity of RNA decreased with increasing proportion of pseudoUridine introduction. In 2008, Katalin Karikó et al. also found that complete replacement of uridine mRNA with pseudoUridine not only greatly reduced the immunogenicity of mRNA, but also improved its stability and enhanced its translational capacity.
N1-methyl-pseudoUridine is a methyl-pseudoUridine, an N1-modified pseudoUridine derivative, a natural modification found in 18S rRNA and tRNA in many organisms. N1-methyl-pseudoUridine has a methyl group at the N1 position, thereby eliminating the additional hydrogen bond donor. PseudoUridine and N1-methyl-pseudoUridine share a key common feature, the C5-C1 bond, which enables rotation between the nucleobase and sugar portions and may contribute to improved base pairing, base stacking and double strand stability. Compared to uridine, N1-methyl-pseudoUridine pairs with A with higher affinity and is less likely to activate PKR, resulting in more efficient translation, and N1-methyl-pseudoUridine, which is structurally similar to pseudoUridine, may also enable mRNA to evade immune responses. In 2015, Oliwia Andries et al. found that complete substitution of uridine with N1-methyl-pseudoUridine reduced the immunogenicity of mRNA and enhanced the protein expression of mRNA more than complete substitution of uridine with pseudoUridine.
Pseudouridine Upstream and Downstream Related Pathways
Metabolism is the general term for all the ordered chemical changes in an organism. Metabolism is the dynamic part of biochemistry and the basis for the existence of biological molecules. The set of interlocking enzymatic reactions that complete a metabolic process is called a metabolic pathway. Metabolic pathways are in communication with each other. Metabolic pathways can intersect with each other through common intermediate metabolites, or they can be articulated through transitional steps. In this way, the various metabolic pathways are linked and form a complex metabolic network.
|Nitrogen metabolism||Nitrogen metabolism describes the biosynthesis of amino acids in plants and microorganisms as well as in mammals and humans.|
|Purine metabolism||Purine metabolism refers to the in vivo synthesis and decomposition of purine derivatives such as the nucleic acid bases adenine and guanine.|
|Galactose metabolism||Galactose can be transported into cells through the cell membrane, a process independent of insulin. Galactose entering cells must be phosphorylated before being metabolized. Under the action of galactokinase, galactose can react with ATP to generate 1-phosphate galactose and ADP.|
|Pyrimidine metabolism||Pyrimidine metabolism refers to a series of metabolic pathways that use pyrimidines (derivatives) as substrates or metabolites.|
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