Integrative Nanopore and Illumina sequencing reveals age-associated tRNA modification and CCA-tail dynamics in yeast
Year: 2026
Type: preprint
Abstract: Aging is characterized by a progressive loss of proteostasis. Transfer RNAs (tRNAs) are essential regulators of translation, yet their dynamics during aging remain poorly understood due to challenges in sequencing highly modified RNAs. Here we present a benchmarked Nanopore direct RNA sequencing (RNA004 chemistry) resource that profiles the Saccharomyces cerevisiae tRNAome during replicative aging at single-molecule resolution. Using in vitro transcribed tRNA controls, we establish modification detection thresholds and validate key findings with orthogonal Illumina sequencing. While overall tRNA abundance remains largely stable, our resource reveals age-associated terminal A cleavage at the 3' CCA tail of mature tRNAs, targeted T-loop and anticodon modification changes, and single-molecule evidence of modification co-occurrence. This dataset provides a resource for exploring tRNA regulation, translation fidelity, and longevity.
Institutions: University of Alabama at Birmingham, University of Virginia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7214521004