title: Mistranslation and its control by tRNA synthetases.
abstract: Aminoacyl tRNA synthetases are ancient proteins that interpret the genetic material in all life forms. They are thought to have appeared during the transition from the RNA world to the theatre of proteins. During translation, they establish the rules of the genetic code, whereby each amino acid is attached to a tRNA that is cognate to the amino acid. Mistranslation occurs when an amino acid is attached to the wrong tRNA and subsequently is misplaced in a nascent protein. Mistranslation can be toxic to bacteria and mammalian cells, and can lead to heritable mutations. The great challenge for nature appears to be serine-for-alanine mistranslation, where even small amounts of this mistranslation cause severe neuropathologies in the mouse. To minimize serine-for-alanine mistranslation, powerful selective pressures developed to prevent mistranslation through a special editing activity imbedded within alanyl-tRNA synthetases (AlaRSs). However, serine-for-alanine mistranslation is so challenging that a separate, genome-encoded fragment of the editing domain of AlaRS is distributed throughout the Tree of Life to redundantly prevent serine-to-alanine mistranslation. Detailed X-ray structural and functional analysis shed light on why serine-for-alanine mistranslation is a universal problem, and on the selective pressures that engendered the appearance of AlaXps at the base of the Tree of Life.
authors.affiliation: Department of Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. schimmel@scripps.edu
authors.forename: Paul
authors.initials: P
authors.lastname: Schimmel
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D000818:Animals; D020134:Catalytic Domain; D024202:Electrophoretic Mobility Shift Assay; D005815:Genetic Code; D006801:Humans; D008322:Mammals; D051379:Mice; D009711:Nucleotides / Q000378:metabolism; D014176:Protein Biosynthesis; D017393:RNA Editing; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism*; D046249:Transfer RNA Aminoacylation
chemical_list: D000596:Amino Acids; D009711:Nucleotides; D012346:RNA, Transfer, Amino Acyl; D000604:Amino Acyl-tRNA Synthetases