Abstract
Transfer RNAs (tRNAs) are the decoders of the protein coding genetic information, as they transfer amino acids into nascent proteins during messenger RNA translation. This pivotal role makes tRNAs a source of translation regulation that can affect protein synthesis. Still, we are beginning to understand the upstream mechanisms regulating tRNA pools themselves. In Dictyostelium discoideum, starvation of a sufficient number of individuals, triggers the development of a coordinated sporulation response denominated the social cycle. By using publicly available transcriptomic, epigenomic, and genomic data, we studied two factors contributing to the regulation of tRNA pools throughout this social cycle. First, the tRNA gene repertoire shows that the compact genome of D. discoideum escapes translational selection as even with a relatively high number of tRNA genes, anticodon and codon frequencies greatly mismatch. This disparity is explained by the overrepresentation of anticodons that can be modified in the wobble position. During the social cycle, the vast majority of tRNA genes lie in nucleosome free regions, indicating that most genes are always contributing to the tRNA pools. However, there is a marked variation in expression levels of the proteins involved in tRNA maturation. This modulation is ultimately mirrored by fine-tuned differential composition of tRNA pools at isodecoder, isoacceptor and isotype levels. Particularly, there is an overall down-regulation in the vegetative to streaming transition. Key elements bypass this down-regulation pattern and taken together, this evidence suggests compensatory mechanisms in tRNA regulation that might rescue translation for the following developmental stages, thus allowing D. discoideum to evolve this remarkable strategy under the pressure of an amino acid scarce environment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-026-00580-0.