tRNA-overlapping long non-coding RNA loci repress codon-biased genes

The functions of most long non-coding RNAs (lncRNAs) are not known. Here, we define a group of "tRNA-overlapping lncRNA" (tROL) genes that are upregulated during in vitro cartilage development. Deletions of tROLs result in changes in the expression of codon-biased genes, where downregulated genes are enriched in codons corresponding to tRNAs overlapping disrupted tROLs. tROL loci are located in gene-dense regions and interact extensively between chromosomes, and tROL whole-gene deletions result in the upregulation of significantly overlapping subsets of genes in the vicinity of tROL loci. Inhibiting the lncRNA transcription and degrading the lncRNA transcripts of a tROL gene downregulates tRNA expression. Taken together, the results suggest that tROL loci coalesce and are dependent on each other's transcription to repress genes in spatial proximity and to activate tRNA expression. Our investigation thus provides insight into a previously uncharacterized role for tROLs as a regulatory bridge between the non-coding and coding genomes.