Misacylated

Misacylated describes a charged transfer RNA (tRNA) that bears the wrong amino acid. In translational biology, a tRNA becomes misacylated when an aminoacyl-tRNA synthetase attaches an incorrect amino acid to a tRNA instead of its cognate one. This error can arise because amino acids share similar structures, and due to limitations in recognition by the enzyme or tRNA identity elements. The fidelity of aminoacylation is the first checkpoint in genetic code translation, preceding codon-anticodon pairing.

Cellular quality control includes editing domains within aminoacyl-tRNA synthetases and separate trans-editing enzymes that hydrolyze the mischarged amino acid from the tRNA (pre-transfer editing, post-transfer editing). For example, alanyl-tRNA synthetase has an editing site that hydrolyzes many mischarged Ser-tRNA^Ala and Cys-tRNA^Ala. Other synthetases and editing factors correct different misacylations; defects in editing increase mistranslation rates and can be deleterious but may also be tolerated under stress or exploited in certain experimental systems.

Impact and research: Misacylation results in mistranslation, potentially inserting wrong amino acids at specific codons and altering protein function. Organisms maintain low but nonzero mistranslation rates; the balance between accuracy and speed of translation, plus cellular stress, influences misacylation frequency. Researchers study misacylation to understand translation fidelity, genetic code evolution, and to enable incorporation of noncanonical amino acids through engineered tRNA/synthetase systems.