AaRS gene family

Genes in the aaRS gene family provide instructions for making enzymes known as aminoacyl-tRNA synthetases. These enzymes are found in all types of cells, where they play an important role in the production (synthesis) of proteins. Protein synthesis begins with a process called transcription. During this process, the information stored in a gene's DNA is transferred to a similar molecule called RNA in the cell nucleus. The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus.

Aminoacyl-tRNA synthetase enzymes are involved in translation, the second step in creating a protein from a gene's instructions. The mRNA interacts with a specialized complex called a ribosome, which "reads" the sequence of mRNA bases (building blocks of RNA and DNA). Each sequence of three bases, called a codon, usually codes for one particular amino acid. (Amino acids are the building blocks of proteins.) A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time. Aminoacyl-tRNA synthetases help attach the amino acid to the tRNA.

During protein synthesis, amino acids are linked together in a specific order. Aminoacyl-tRNA synthetase enzymes each play a role in adding a specific amino acid at the proper place in a protein's chain of amino acids. For example, the enzyme produced from the GARS gene, glycyl-tRNA synthetase, helps add the amino acid glycine at the proper place in the protein sequence.

Nerve cells (neurons) seem to be particularly sensitive to mutations in aminoacyl-tRNA synthetase genes, and several of these mutations have been associated with neurological disorders. Researchers suggest that genes in this family may have additional functions in neurons that are impaired by some of these mutations. Another possibility is that some mutations may result in an aminoacyl-tRNA synthetase that is folded improperly, which can allow this protein to build up to toxic levels in neurons. The accumulation of misfolded proteins is associated with several neurodegenerative diseases, such as Alzheimer disease and prion diseases.