Human mitochondrial TyrRS disobeys the tyrosine identity rules.
Human tyrosyl-tRNA synthetase from mitochondria (mt-TyrRS) presents dual sequence features characteristic of eubacterial and archaeal TyrRSs, especially in the region containing amino acids recognizing the N1-N72 tyrosine identity pair. This would imply that human mt-TyrRS has lost the capacity to discriminate between the G1-C72 pair typical of eubacterial and mitochondrial tRNATyr and the reverse pair C1-G72 present in archaeal and eukaryal tRNATyr. This expectation was verified by a functional analysis of wild-type or mutated tRNATyr molecules, showing that mt-TyrRS aminoacylates with similar catalytic efficiency its cognate tRNATyr with G1-C72 and its mutated version with C1-G72. This provides the first example of a TyrRS lacking specificity toward N1-N72 and thus of a TyrRS disobeying the identity rules. Sequence comparisons of mt-TyrRSs across phylogeny suggest that the functional behavior of the human mt-TyrRS is conserved among all vertebrate mt-TyrRSs.
Bonnefond
Luc
L
UPR 9002 du CNRS-IBMC, 15 rue René Descartes, F-67084 Strasbourg, France.
Frugier
Magali
M
Giegé
Richard
R
Rudinger-Thirion
Joëlle
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D020134:Catalytic Domain; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D012365:RNA, Transfer, Tyr / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*; D014448:Tyrosine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism*
D012365:RNA, Transfer, Tyr; D014443:Tyrosine; D014448:Tyrosine-tRNA Ligase