一种现存的氨基酰-tRNA合成酶（AaLeuRS）具有祖先编校特性

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近期，生化与细胞所王恩多研究组在《RNA》杂志公布了最新研究发现：一种现存的具有祖先编校特性的氨基酰-tRNA合成酶，揭示了AaLeuRS可能有着比IleRS及ValRS更为原始的编校特性，其编校结构域可能保留了三种酶共同的祖先编校结构域，该发现为研究氨基酰-tRNA合成酶催化特异性进化提供了的重要线索。

  氨基酰-tRNA合成酶(aaRS)的催化特异性对遗传信息的准确传递十分重要。亮氨酰-、异亮氨酰-及缬氨酰-tRNA合成酶（LeuRS, IleRS, ValRS）通过“转移后编校”水解错误的氨基酰化产物。这类aaRS的编校结构域是插入活性中心称为CP1(Connective Peptide 1)的插入肽段。王恩多研究组的研究结果表明，来源于原始的超嗜热菌Aquifex aeolicus的LeuRS（AaLeuRS）能编校这一类酶催化产生的氨基酰化产物或误氨基酰化产物，例如Ile-tRNAIle, Val-tRNAile, Val-tRNAVal, Thr-tRNAVal和Ile-tRNALeu。

  为了进一步研究AaLeuRS这一广泛的编校活性，研究者们设计了携带三重识别元件的RNA小螺旋(minihelixLIV)以模拟原始的tRNA，研究了AaLeuRS，大肠杆菌IleRS和 LeuRS, 枯草杆菌ValRS单独的CP1肽段编校误氨基酰化小螺旋的能力。结果表明只有AaLeuRS单独的CP1肽段可以水解误氨基酰化的小螺旋，例如Ile-minihelixLIV, Val-minihelixLIV 和Thr-minihelixLIV，而IleRS及ValRS的单独的CP1肽段则不能。这些结果说明AaLeuRS可能有着比IleRS及ValRS更为原始的编校特性，其编校结构域可能保留了三种酶共同的祖先编校结构域，它应当具有非专一性的编校功能。

部分英文原文：

Published online before print November 9, 2006, 10.1261/rna.228707

REPORT
A present-day aminoacyl-tRNA synthetase with ancestral editing properties
Bin Zhu1, Ming-Wei Zhao1, Gilbert Eriani2, and En-Duo Wang1

1 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, People's Republic of China
2 UPR9002 du CNRS, ARN, Université Louis Pasteur, 67084 Strasbourg, France


Leucyl-, isoleucyl-, and valyl-tRNA synthetases form a subgroup of related aminoacyl-tRNA synthetases that attach similar amino acids to their cognate tRNAs. To prevent amino acid misincorporation during translation, these enzymes also hydrolyze mischarged tRNAs through a post-transfer editing mechanism. Here we show that LeuRS from the deep-branching bacterium Aquifex aeolicus edits the complete set of aminoacylated tRNAs generated by the three enzymes: Ile-tRNAIle, Val-tRNAile, Val-tRNAVal, Thr-tRNAVal, and Ile-tRNALeu. This unusual enlarged editing property was studied in a model of a primitive editing system containing a composite minihelix carrying the triple leucine, isoleucine, and valine identity mimicking the primitive tRNA precursor. We found that the freestanding LeuRS editing domain can edit this precursor in contrast to IleRS and ValRS editing domains. These results suggest that A. aeolicus LeuRS carries editing properties that seem more primitive than those of IleRS and ValRS. They suggest that the A. aeolicus editing domain has preserved the ambiguous editing property from the ancestral common editing domain or, alternatively, that this plasticity results from a specific metabolic adaptation.


Keywords: Aminoacyl-tRNA synthetases; evolution; proofreading