Quantitative tRNA-sequencing uncovers metazoan tissue-specific tRNA regulation

Otis Pinkard, Sean McFarland, Thomas Sweet () and Jeff Coller ()
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Otis Pinkard: Case Western Reserve University
Sean McFarland: Tevard Biosciences, LabCentral
Thomas Sweet: Case Western Reserve University
Jeff Coller: Johns Hopkins School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Transfer RNAs (tRNA) are quintessential in deciphering the genetic code; disseminating nucleic acid triplets into correct amino acid identity. While this decoding function is clear, an emerging theme is that tRNA abundance and functionality can powerfully impact protein production rate, folding, activity, and messenger RNA stability. Importantly, however, the expression pattern of tRNAs is obliquely known. Here we present Quantitative Mature tRNA sequencing (QuantM-tRNA seq), a technique to monitor tRNA abundance and sequence variants secondary to RNA modifications. With QuantM-tRNA seq, we assess the tRNA transcriptome in mammalian tissues. We observe dramatic distinctions in isodecoder expression and known tRNA modifications between tissues. Remarkably, despite dramatic changes in tRNA isodecoder gene expression, the overall anticodon pool of each tRNA family is similar across tissues. These findings suggest that while anticodon pools appear to be buffered via an unknown mechanism, underlying transcriptomic and epitranscriptomic differences suggest a more complex tRNA regulatory landscape.

Date: 2020
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DOI: 10.1038/s41467-020-17879-x

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