AI & dataCellsPreprint

Yeast tRNAs show age-associated tail cleavage and modifications

Using direct RNA sequencing in replicatively aging yeast, researchers mapped single-molecule tRNA dynamics, revealing stable total abundance alongside targeted modifications and 3' CCA-tail cleavage.

bioRxiv

In the budding yeast Saccharomyces cerevisiae, researchers tracked tRNA dynamics during replicative aging at single-molecule resolution. Aging involves a progressive loss of proteostasis, and transfer RNAs serve as key regulators of translation, but sequencing their highly modified structures has posed technical challenges. To profile the aging yeast tRNAome, the authors combined Nanopore direct RNA sequencing using RNA004 chemistry with orthogonal Illumina sequencing. They established modification detection thresholds using in vitro transcribed tRNA controls. Although overall tRNA abundance remained largely stable, the data revealed age-associated terminal A cleavage at the 3’ CCA tail of mature tRNAs. The platform also identified targeted modification changes within the anticodon and T-loop regions, along with single-molecule evidence of modification co-occurrence.

Why it matters

The findings offer a resource for studying how post-transcriptional tRNA alterations and specific modification patterns may influence translation fidelity and longevity as cells age.

Caveats

The results are limited to single-celled yeast during replicative aging. Additionally, this work is reported in a preprint and has not yet completed peer review.

The paper

Integrative Nanopore and Illumina sequencing reveals age-associated tRNA modification and CCA-tail dynamics in yeast

University of Alabama at Birmingham

bioRxiv · 27 Sep 2026 · Preprint, not peer-reviewed

doi.org/10.64898/2026.09.22.753482