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1.
RNA ; 29(9): 1379-1387, 2023 09.
Article in English | MEDLINE | ID: mdl-37221013

ABSTRACT

Under certain circumstances, any of the three termination codons can be read through by a near-cognate tRNA; i.e., a tRNA whose two out of three anticodon nucleotides base pair with those of the stop codon. Unless programed to synthetize C-terminally extended protein variants with expanded physiological roles, readthrough represents an undesirable translational error. On the other side of a coin, a significant number of human genetic diseases is associated with the introduction of nonsense mutations (premature termination codons [PTCs]) into coding sequences, where stopping is not desirable. Here, the tRNA's ability to induce readthrough opens up the intriguing possibility of mitigating the deleterious effects of PTCs on human health. In yeast, the UGA and UAR stop codons were described to be read through by four readthrough-inducing rti-tRNAs-tRNATrp and tRNACys, and tRNATyr and tRNAGln, respectively. The readthrough-inducing potential of tRNATrp and tRNATyr was also observed in human cell lines. Here, we investigated the readthrough-inducing potential of human tRNACys in the HEK293T cell line. The tRNACys family consists of two isoacceptors, one with ACA and the other with GCA anticodons. We selected nine representative tRNACys isodecoders (differing in primary sequence and expression level) and tested them using dual luciferase reporter assays. We found that at least two tRNACys can significantly elevate UGA readthrough when overexpressed. This indicates a mechanistically conserved nature of rti-tRNAs between yeast and human, supporting the idea that they could be used in the PTC-associated RNA therapies.


Subject(s)
Cysteine , Saccharomyces cerevisiae , Humans , Codon, Terminator/genetics , Cysteine/genetics , Cysteine/metabolism , HEK293 Cells , Saccharomyces cerevisiae/genetics , RNA, Transfer, Cys/metabolism , RNA, Transfer, Trp/metabolism , RNA, Transfer, Tyr , RNA, Transfer/genetics , RNA, Transfer/metabolism , Anticodon , Codon, Nonsense/genetics , Protein Biosynthesis
2.
PLoS One ; 12(9): e0185243, 2017.
Article in English | MEDLINE | ID: mdl-28945773

ABSTRACT

Laterality is a well described phenomenon in domestic dogs. It was shown that dogs, under calm Earth's magnetic field conditions, when marking their home ranges, tend to head about north- or southwards and display thus magnetic alignment. The question arises whether magnetic alignment might be affected or even compromised by laterality and vice versa. We tested the preference of dogs to choose between two dishes with snacks that were placed left and right, in different compass directions (north and east, east and south, south and west or west and north) in front of them. Some dogs were right-lateral, some left-lateral but most of them were ambilateral. There was a preference for the dish placed north compared to the one placed east of the dog ("pull of the north"). This effect was highly significant in small and medium-sized breeds but not in larger breeds, highly significant in females, in older dogs, in lateralized dogs but less significant or not significant in males, younger dogs, or ambilateral dogs. Laterality and "pull of the north" are phenomena which should be considered in diverse tasks and behavioral tests with which dogs or other animals might be confronted. The interaction and possible conflict between lateralization and "pull of the north" might be also considered as a reason for shifted magnetic alignment observed in different animal species in different contexts.


Subject(s)
Dogs/physiology , Dogs/psychology , Functional Laterality/physiology , Animals , Behavior, Animal/physiology , Female , Magnetic Fields , Male , Orientation, Spatial/physiology
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