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

Area of Science:

• Genomics
• Molecular Biology
• RNA Biology

Background:

• The functions of most long non-coding RNAs (lncRNAs) remain largely unknown.
• Understanding lncRNA roles is critical for deciphering gene regulation.
• lncRNAs are increasingly recognized for their diverse regulatory functions.

Purpose of the Study:

• To characterize a novel class of lncRNAs, termed tRNA-overlapping lncRNAs (tROLs).
• To investigate the function of tROLs in cartilage development and gene expression.
• To elucidate the regulatory mechanisms involving tROLs, tRNA expression, and protein-coding genes.

Main Methods:

• Identification and characterization of tROL genes upregulated during in vitro cartilage development.
• Analysis of gene expression changes following tROL whole-gene deletions.
• Investigation of codon bias in downregulated genes.
• Assessment of tRNA expression levels upon tROL inhibition or degradation.
• Chromosomal interaction analysis of tROL loci.

Main Results:

• tROL genes are upregulated during in vitro cartilage development.
• tROL deletions alter the expression of codon-biased genes, particularly those with codons corresponding to overlapping tRNAs.
• tROL loci are located in gene-dense regions and exhibit inter-chromosomal interactions.
• tROL whole-gene deletions lead to upregulation of neighboring genes.
• Inhibition or degradation of tROL transcripts results in decreased tRNA expression.

Conclusions:

• tROL loci function collectively, relying on mutual transcription to regulate nearby genes and modulate tRNA expression.
• tROLs act as a regulatory link between the non-coding and coding genomes.
• This study reveals a previously uncharacterized role for tROLs in gene regulation and tRNA homeostasis.