Evolutionary gain of highly divergent tRNA specificities by two isoforms of human histidyl-tRNA synthetase
- 340 Downloads
The discriminator base N73 is a key identity element of tRNAHis. In eukaryotes, N73 is an “A” in cytoplasmic tRNAHis and a “C” in mitochondrial tRNAHis. We present evidence herein that yeast histidyl-tRNA synthetase (HisRS) recognizes both A73 and C73, but somewhat prefers A73 even within the context of mitochondrial tRNAHis. In contrast, humans possess two distinct yet closely related HisRS homologues, with one encoding the cytoplasmic form (with an extra N-terminal WHEP domain) and the other encoding its mitochondrial counterpart (with an extra N-terminal mitochondrial targeting signal). Despite these two isoforms sharing high sequence similarities (81% identity), they strongly preferred different discriminator bases (A73 or C73). Moreover, only the mitochondrial form recognized the anticodon as a strong identity element. Most intriguingly, swapping the discriminator base between the cytoplasmic and mitochondrial tRNAHis isoacceptors conveniently switched their enzyme preferences. Similarly, swapping seven residues in the active site between the two isoforms readily switched their N73 preferences. This study suggests that the human HisRS genes, while descending from a common ancestor with dual function for both types of tRNAHis, have acquired highly specialized tRNA recognition properties through evolution.
KeywordsAminoacyl-tRNA synthetase Evolution Phylogenetic analysis Protein synthesis Subfunctionalization tRNA
Green fluorescence protein
Mitochondrial targeting signal
Polymerase chain reaction
Yeast extract peptone glycerol.
This work was supported by Grants MOST 103-2311-B-008-003-MY3, MOST 103-2923-B-008-001-MY3, and NSC 102-2311-B-008-004-MY3 (to C.C.W.) from the Ministry of Science and Technology (Taipei, Taiwan).
- 24.Chang CP, Chang CY, Lee YH, Lin YS, Wang CC (2015) Divergent alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora descended from a common ancestor through whole-genome duplication followed by asymmetric evolution. Mol Cell Biol 35(13):2242–2253. doi: 10.1128/MCB.00018-15 CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K, Willert RA, Achilly NP, Cassidy RP, Fiorentini CJ, Heiken KF, Lawrence JJ, Mahoney MH, Miller CJ, Nair DT, Politi KA, Worcester KN, Setton RA, Dipiazza R, Sherman EA, Eastman JT, Francklyn C, Robey-Bond S, Rider NL, Gabriel S, Morton DH, Strauss KA (2012) Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One 7(1):e28936. doi: 10.1371/journal.pone.0028936 CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Pierce SB, Chisholm KM, Lynch ED, Lee MK, Walsh T, Opitz JM, Li W, Klevit RE, King MC (2011) Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome. Proc Natl Acad Sci USA 108(16):6543–6548. doi: 10.1073/pnas.1103471108 CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Zhou JJ, Wang F, Xu Z, Lo WS, Lau CF, Chiang KP, Nangle LA, Ashlock MA, Mendlein JD, Yang XL, Zhang M, Schimmel P (2014) Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for autoantibodies in inflammatory myositis. J Biol Chem 289(28):19269–19275. doi: 10.1074/jbc.C114.571026 CrossRefPubMedPubMedCentralGoogle Scholar
- 45.Horton P, Park KJ, Obayashi T, Fujita N, Harada H, Adams-Collier CJ, Nakai K (2007) WoLF PSORT: protein localization predictor. Nucleic Acids Res 35 (Web Server issue):W585–587. doi: 10.1093/nar/gkm259