Ancestral AlaX editing enzymes for control of genetic code fidelity are not tRNA-specific.
Accurate protein synthesis requires the hydrolytic editing of tRNAs incorrectly aminoacylated by aminoacyl-tRNA synthetases (ARSs). Recognition of cognate tRNAs by ARS is less error-prone than amino acid recognition, and, consequently, editing domains are generally believed to act only on the tRNAs cognate to their related ARSs. For example, the AlaX family of editing domains, including the editing domain of alanyl-tRNA synthetase and the related free-standing trans-editing AlaX enzymes, are thought to specifically act on tRNA(Ala), whereas the editing domains of threonyl-tRNA synthetases are specific for tRNA(Thr). Here we show that, contrary to this belief, AlaX-S, the smallest of the extant AlaX enzymes, deacylates Ser-tRNA(Thr) in addition to Ser-tRNA(Ala) and that a single residue is important to determine this behavior. Our data indicate that promiscuous forms of AlaX are ancestral to tRNA-specific AlaXs. We propose that former AlaX domains were used to maintain translational fidelity in earlier stages of genetic code evolution when mis-serylation of several tRNAs was possible.
From the Institute for Research in Biomedicine, c/ Baldiri Reixac 10, 08028 Barcelona, Catalonia, Spain.
Eva Maria
EM
Novoa
the Department of Chemistry and Biochemistry, Center for RNA Biology, Ohio State University, Columbus, Ohio 43210.
Oscar
O
Vargas-Rodriguez
From the Institute for Research in Biomedicine, c/ Baldiri Reixac 10, 08028 Barcelona, Catalonia, Spain.
Stefanie
S
Lange
the Department of Chemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan, and.
Yuki
Y
Goto
the Department of Chemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan, and.
Hiroaki
H
Suga
the Department of Chemistry and Biochemistry, Center for RNA Biology, Ohio State University, Columbus, Ohio 43210.
Karin
K
Musier-Forsyth
From the Institute for Research in Biomedicine, c/ Baldiri Reixac 10, 08028 Barcelona, Catalonia, Spain, the Catalan Institution for Research and Advanced Studies, Passeig Lluís Companys 23, 08010 Barcelona, Catalonia, Spain lluis.ribas@irbbarcelona.org.
Lluís
L
Ribas de Pouplana
D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005815:Genetic Code; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D043903:Pyrococcus abyssi / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D043902:Pyrococcus horikoshii / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017393:RNA Editing; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D019843:Archaeal Proteins; D011994:Recombinant Proteins; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases
AlaX; Aminoacyl tRNA Synthetase; Genetic Code; Mistranslation; Proofreading; Protein Evolution; RNA Editing; phylogenetics; tRNA