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. 2024 Sep 12;52(18):11158–11176. doi: 10.1093/nar/gkae776

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© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 7. — RTP801 downregulation in hippocampal neurons prevents accumulation of intron-containing pre-tRNAs in 5xFAD mice. The percentage of normalized counts for pre-tRNA is depicted, classified by amino acid and anticodon. Different pre-tRNA species within an isodecoder family are represented. Pre-tRNA species in red do not have an intron and are included as a control. Since all tyrosine-accepting pre-tRNAs have intron, pre-tRNA-Phe-GAA-1 (also accepts an aromatic amino acid) was included as a control. Relative expression of pre-tRNA-Arg-TCT (A), pre-tRNA-Ile-TAT (B), pre-tRNA-Leu-CAA (C), and pre-tRNA-Tyr-GTA (D) (pre-tRNA-Arg-TCT-1–1: genotype effect: F_{(1, 14)} = 4.942, P = 0.0432, treatment effect: F_{(1, 14)} = 20.64, P = 0.0005; pre-tRNA-Arg-TCT-2–1: genotype effect: F_{(1, 13)} = 15.37, P = 0.0018, interaction effect: F_{(1, 13)} = 14.52, P = 0.0022; pre-tRNA-Arg-TCT-3–1: interaction effect: F_{(1, 13)} = 4.876, P = 0.0458; pre-tRNA-Ile-TAT-1–1: genotype effect: F_{(1, 13)} = 11.69, P = 0.0046, treatment effect: F_{(1, 13)} = 5.093, P = 0.0419, interaction effect: F_{(1, 13)} = 12.52, P = 0.0036; tRNA-Ile-TAT-2: genotype effect: F_{(1, 13)} = 6.102, P = 0.0281; pre-tRNA-Leu-CAA-2–1: genotype effect: F_{(1, 14)} = 10.75, P = 0.0055, treatment effect: F_{(1, 14)} = 7.621, P = 0.0153, interaction effect: F_{(1, 14)} = 10.46, P = 0.0060; pre-tRNA-Leu-CAA-3–1: genotype effect: F_{(1, 14)} = 5.081, P = 0.0407, interaction effect: F_{(1, 14)} = 4.977, P = 0.0426; pre-tRNA-Leu-CAA-4–1: genotype effect: F_{(1, 13)} = 4.953, P = 0.0444, treatment effect: F_{(1, 13)} = 7.206, P = 0.0187, interaction effect: F_{(1, 13)} = 11.05, P = 0.0055; pre-tRNA-Tyr-GTA-2–1: genotype effect: F_{(1, 14)} = 17.27, P = 0.0010, treatment effect: F_{(1, 14)} = 17.11, P = 0.0010, interaction effect: F_{(1, 14)} = 22.18, P = 0.0003; pre-tRNA-Tyr-GTA-3: treatment effect: F_{(1, 14)} = 5.218, P = 0.0385). Data are means ± SEM. In all comparisons two-way ANOVA with Tukey’s post hoc test was performed. Each value represents one animal. Values were excluded when they were classified as outliers with either the ROUT or the Grubbs’ test from Graphpad Prism software; *P < 0.05, **P < 0.01, and ***P < 0.001.