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bioRxiv · 10.1101/870352

The Genomic Loci of Specific Human tRNA Genes Exhibit Ageing-Related DNA Hypermethylation

Acton, R. J.·Yuan, W.·Gao, F.·Xia, Y.·Bourne, E.·Wozniak, E.·Bell, J.·Lillycrop, K.·Wang, J.·Dennison, E.·Harvey, N.·Mein, C. A.·Spector, T. D.·Hysi, P. G.·Cooper, C.·Bell, C. G.
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Abstract

The epigenome deteriorates with age, potentially impacting on ageing-related disease. Here, we interrogate the DNA methylation state of the genomic loci of human tRNA. Whilst arising from only ~46kb (<0.002% genome), this information transfer machinery is the second most abundant cellular transcript. tRNAs also control metabolic processes known to affect ageing, through core translational and additional regulatory roles. We identified a genomic enrichment for age-related DNA hypermethylation at tRNA loci. Analysis in 4,350 MeDIP-seq peripheral-blood DNA methylomes (16-82 years), classified 44 and 21 hypermethylating specific tRNAs at study- and genome-wide significance, respectively, contrasting with 0 hypomethylating. Validation and replication (450k array & independent targeted Bisuphite-sequencing) supported thehypermethylation of this functional unit. The strongest consistent signals, also independent of major cell-type change, occur in tRNA-iMet-CAT-1-4 and tRNA-Ser-AGA-2-6. This study is this first comprehensive evaluation of the genomic DNA methylation state of human tRNA genes and reveals a discreet hypermethylation with advancing age.

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Acton, R. J., Yuan, W., Gao, F., Xia, Y., Bourne, E., Wozniak, E., Bell, J., Lillycrop, K., Wang, J., Dennison, E., Harvey, N., Mein, C. A., Spector, T. D., Hysi, P. G., Cooper, C., Bell, C. G.. 2019-12-10. The Genomic Loci of Specific Human tRNA Genes Exhibit Ageing-Related DNA Hypermethylation. https://doi.org/10.1101/870352

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