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The highly conserved intron of tyrosine tRNA is critical for m1A58 modification and controls the integrated stress response

Catherine J Stuart,Jennifer E. Hurtig,Talia Tzadikario,Niki K Thomas,Miten Jain,A. van Hoof

Published 2025 in Proceedings of the National Academy of Sciences of the United States of America

ABSTRACT

Significance tRNAs are required to translate the genetic code into protein sequence. tRNAs also contain more modifications than any other RNA. Although tRNA introns are universal in eukaryotes and distinct from other introns, their function has remained unknown. Here, we reveal that the intron of tyrosine-decoding tRNA is the most widely conserved among eukaryotes and is important for methylation of a specific position in this pre-tRNA. The absence of this intron perturbs cellular homeostasis and induces the integrated stress response. We propose that the enzyme responsible for this modification recognizes and modifies the intron-containing precursor of this tRNA but cannot modify the spliced tRNA. This provides a plausible reason for the conservation of tRNA introns across eukaryotes.

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