Aminoacyl-tRNA biosynthesis and neurodevelopment in DCDA-D twins
Lower cysteine, threonine, leucine, and alanyl-proline, involved in aminoacyl-tRNA biosynthesis, were associated with worse communication, fine motor, and problem-solving in both larger and smaller twins of DCDA-D pairs. Aminoacyl-tRNAs are translation substrates and pivotal in interpreting how genetic nucleotides are translated into amino acids. This is mainly achieved by the direct attachment of an amino acid to the corresponding tRNA by a specific aminoacyl-tRNA synthetase (ARS).35 An increasing number of studies have linked pathogenic variation in ARS with neurological diseases.36-39 Children with ARS deficiencies were observed with central nervous system symptoms, intrauterine growth restriction, and failure to thrive. These adverse outcomes of ARS deficiency could have resulted from reduced aminoacylation activity, translational inefficiency, and compromised proliferation.40 Furthermore, several studies have reported that ARS senses amino acids for mTOR signaling, which plays a critical role in neural development. The PI3K-Akt-mTOR pathway is essential for neurogenesis from neural stem cells and subsequent migration and maturation.41,42 Liang et al . showed the inhibition of the Akt-mTOR signaling pathway, disrupting neurogenesis and inducing autophagy.43 Thus, we speculate that the downregulation of amino acids, such as cysteine, threonine, and leucine associated with discordant growth in uteromay be an indicator of dysregulation of aminoacyl-tRNA biosynthesis, which participates in modulating decreased translation and consequently decreased protein production at a crucial time during brain development.