The Human tRNA Story: A Complex Epigenomic Landscape Unfolds

Despite mounting evidence for the importance of tRNA regulation in diverse biological processes, relatively little is known about the regulation of specific tRNA loci in complex multicellular organisms. In humans, as in most eukaryotes, tRNA genes comprise one of the largest single gene families that produce more transcripts than any other type of RNA. However, estimates of transcriptional activity of the 500+ individual human tRNA genes across multiple tissue types are almost entirely absent due to difficulty measuring specific tRNA transcript abundance on a large scale, as well as uncertain assignment of most transcripts among identical loci. I will present our new analyses of human tRNA genes using a combination of (1) specialized tRNA-seq transcriptional analyses (ARM-seq), (2) epigenetic data revealing transcription activation states associated with each gene over a range of cell types, and (3) and novel insights derived from a new version of tRNAscan-SE, which has been the standard for tRNA gene prediction for two decades. Enhancements to tRNAscan-SE include development of over 100 new, specialized tRNA covariance models which enable improved classification of eukaryotic, bacterial, archaeal, and mitochondrial tRNAs. These new computational analyses and experimental data are being integrated into the Genomic tRNA Database to provide the most comprehensive view of tRNA form & function, enabling new insights and suggesting new studies in tRNA and tRNA-derived small RNA research. Presentation: 1:19:1