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• W2145657918 endingPage "260" @default.
• W2145657918 startingPage "254" @default.
• W2145657918 abstract "The A3243G mutation within the human mitochondrial (hs mt) tRNA Leu(UUR) gene is associated with maternally inherited deafness and diabetes (MIDD) and other mitochondrial encephalopathies. One of the most pronounced structural effects of this mutation is the disruption of the native structure through stabilization of a high-affinity dimeric complex. We conducted a series of studies that address the structural properties of this tRNA dimer, and we assessed its formation under physiological conditions. Enzymatic probing was used to directly define the dimeric interface for the complex, and a discrete region of the D-stem and loop of hs mt tRNA Leu(UUR) was identified. The dependence of dimerization on magnesium ions and temperature was also tested. The formation of the tRNA dimer is influenced by temperature, with dimerization becoming more efficient at physiological temperature. Complexation of the mutant tRNA is also affected by the amount of magnesium present, and occurs at concentrations present intracellularly. Terbium probing experiments revealed a specific metal ion-binding site localized at the site of the A3243G mutation that is unique to the dimer structure. This metal ion-binding site presents a striking parallel to dimeric complexes of viral RNAs, which use the same hexanucleotide sequence for complexation and feature a similarly positioned metal ion-binding site within the dimeric structure. Taken together, these results indicate that the unique dimeric complex formed by the hs mt tRNA Leu(UUR) A3243G mutant exhibits interesting similarities to biological RNA dimers, and may play a role in the loss of function caused by this mutation in vivo." @default.
• W2145657918 created "2016-06-24" @default.
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• W2145657918 date "2005-02-08" @default.
• W2145657918 modified "2023-09-23" @default.
• W2145657918 title "Structural probing of a pathogenic tRNA dimer" @default.
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• W2145657918 doi "https://doi.org/10.1261/rna.7143305" @default.
• W2145657918 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1370715" @default.
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• W2145657918 hasPublicationYear "2005" @default.
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