Repurposing tRNA isodecoders for non-canonical functions via tRNA cleavage
Biorxiv : the Preprint Server for Biology
|September 16, 2024
Summary
Transfer RNAs (tRNAs) have hundreds of genes in humans, but their purpose is unclear. This study shows that specific tRNA isodecoders, differing by one nucleotide, can be repurposed for non-canonical functions through cleavage into distinct tRNA-derived RNAs (tDRs).
Area of Science:
- Molecular Biology
- Genetics
- RNA Biology
Background:
- The human genome contains numerous transfer RNA (tRNA) genes, but the biological significance of this redundancy is not fully understood.
- While tRNA isoacceptor pool expression changes are linked to protein synthesis demands, variations in individual tRNA isodecoder expression remain poorly understood.
- tRNAs are known to participate in non-canonical functions beyond protein synthesis, including the generation of tRNA-derived RNAs (tDRs).
Purpose of the Study:
- To investigate the functional consequences of nucleotide variations within tRNA isodecoders.
- To explore the role of tRNA cleavage in generating distinct tRNA-derived RNAs (tDRs) with potentially different bioactivities.
- To propose a model for the functional repurposing of specific tRNA isodecoders for non-canonical roles.
Main Methods:
- Analysis of tRNA isodecoder expression variations.
- Investigating the cleavage of specific tRNA isodecoder sets (tRNA His-GTG, tRNA Gly-GCC, tRNA Cys-GCA) by ribonucleases.
- Assessing the differential activity of generated 5'-tRNA-derived stress-induced RNAs (tiRNAs) on mRNA reporter translation.
Main Results:
- tRNA isodecoders differing by a single nucleotide can yield distinct sets of tiRNAs.
- These nucleotide variations lead to differential bioactivities of the resulting tiRNAs.
- Specific isodecoder sets, including tRNA His-GTG, tRNA Gly-GCC, and tRNA Cys-GCA, were shown to produce tiRNAs with varying translational regulatory effects.
Conclusions:
- Cleavage of specific tRNA isodecoders can functionally repurpose them for non-canonical roles.
- Nucleotide variations within isodecoders are critical for generating distinct tDRs with variable bioactivities.
- This mechanism provides a novel way to expand the functional repertoire of tRNA genes beyond canonical translation.
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