Enjoy the Silence: Nearly Half of Human tRNA Genes Are Silent

Transfer RNAs (tRNAs) are key components of the translation machinery. They read codons on messenger RNAs (mRNAs) and deliver the appropriate amino acid to the ribosome for protein synthesis. The human genome encodes more than 500 tRNA genes but their individual contribution to the cellular tRNA pool is unclear. In recent years, novel methods were developed to improve the quantification of tRNA gene expression, most of which rely on next-generation sequencing such as small RNA-Seq applied to tRNAs (tRNA-Seq). In a previous study, we presented a bioinformatics strategy to analyse tRNA-Seq datasets that we named ‘isodecoder-specific tRNA gene contribution profiling’ (Iso-tRNA-CP). Using Iso-tRNA-CP, we showed that tRNA gene expression is cell type- and tissue-specific and that this process can regulate tRNA-derived fragments abundance. An additional observation that stems from that work is that approximately half of human tRNA genes appeared silent or poorly expressed. In this commentary, I discuss this finding in light of the current literature and speculate on potential functions that transcriptionally silent tRNA genes may play. Studying silent tRNA genes may offer a unique opportunity to unravel novel mechanisms of cell regulation associated to tRNA biology.