Quantitative tRNA-sequencing uncovers metazoan tissue-specific tRNA regulation

• Published in: Nature communications 2020-08, Vol.11 (1), p.4104-4104, Article 4104
• Main Authors: Pinkard, Otis, McFarland, Sean, Sweet, Thomas, Coller, Jeff
• Format: Article
• Language: English
• Subjects: 38; 38/91; 631/1647/514/2254; 631/337/574/1793; Amino acids; Animals; Anticodon - genetics; Blotting, Northern; Decoding; Female; Folding; Gene expression; Genetic code; High-Throughput Nucleotide Sequencing - methods; Humanities and Social Sciences; Male; Mice; Mice, Inbred C57BL; mRNA stability; multidisciplinary; Nucleic acids; Nucleotide sequence; Protein folding; Proteins; Relative abundance; Ribonucleic acid; RNA; RNA Stability - genetics; RNA Stability - physiology; RNA, Messenger - metabolism; RNA, Transfer - genetics; RNA, Transfer - metabolism; Science; Science (multidisciplinary); Stability; Tissues; Transcriptomics; tRNA
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-17879-x

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 Quant itative M ature tRNA seq uencing (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. The relative abundance of specific tRNA can impact protein production rate, folding, and messenger RNA stability. Here the authors describe QuantM-tRNA seq — a method to monitor tRNA abundance and sequence variants — and uncover distinctions in isodecoder expression between tissues that are independent of the anticodon pool of each tRNA family.