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Studying of RNA-protein interactions between a mutant form of glycyl-tRNA synthetase associated with neurodegenerative diseases and IRES type I.

Vinogradova, E.; Mikhaylina, A.; Nikonov, O.; Nikonova, E.

2023-03-30 molecular biology
10.1101/2023.03.29.534367 bioRxiv
Show abstract

Aminoacyl-tRNA synthetases (aaRS) are the main enzymes of protein biosynthesis. Human glycyl-tRNA synthetase, in addition to the main function of amino acid transfer to the corresponding tRNA molecules, is also involved in the initiation of IRES I translation. All members of the enterovirus genus have this type of IRES. It is also known that the presence of point mutations in aaRS leads to the occurrence of diseases in which peripheral nerves are affected. One such disorder of the nervous system is the incurable neurodegenerative disorder Charcot-Marie-Tooth (CMT). The most studied enzyme whose mutations cause CMT is glycyl-tRNA synthetase (GlyRS). In this work, we tested the ability of various mutant forms of glycyl-tRNA synthetase associated with Charcot-Marie-Tooth syndrome to form a stable complex with IRES I. It turned out that neither catalytic activity nor the ability to form a dimer are necessary for the interaction of GlyRS with IRES.

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