Trans-oligomerization of duplicated aminoacyl-tRNA synthetases maintains genetic code fidelity under stress.
Trans-oligomerization of duplicated aminoacyl-tRNA synthetases maintains genetic code fidelity under stress.
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DOI：
10.1093/nar/gkv1020
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发表时间：
2015-11-16
影响因子：
14.9
通讯作者：
Luque I
中科院分区：
文献类型：
--
作者：
Rubio MÁ;Napolitano M;Ochoa de Alda JA;Santamaría-Gómez J;Patterson CJ;Foster AW;Bru-Martínez R;Robinson NJ;Luque I
氨基酰-tRNA合成酶(AARs)通过产生带电的tRNAs在破译遗传信息中起着关键作用，并配备了校对机制来确保tRNAs与其同源氨基酸的正确配对。复制的AARs在自然界中非常常见，在26,837个基因组中观察到25,913个案例。许多AARs的寡聚性提出了一个问题，即复制酶的功能和寡聚化是如何组织的。我们在一个原核生物模型中描述了这个问题，该生物表达两种不同的苏氨酰-tRNA合成酶，负责合成Thr-tRNathr：一个准确且结构性表达(T1)，另一个(T2)校对活性受损，这也会产生错误的Ser-tRNathr。低锌促进二聚体T1解离成失去氨酰化活性的单体，同时诱导T2，T2在低锌条件下对氨基酰化反应是活跃的。T2要么与T1亚基形成同源二聚体，要么与T1亚基形成异源二聚体，从而在反式中提供必要的校对活性。这些发现证明，在具有重复基因的生物体中，细胞可以协调AARS寡聚体的组装，以满足细胞在每种情况下的必需品。我们认为，复制的AARs的受控齐聚是一种适应性机制，可以潜在地扩展到具有复制的AARs的过多的生物体。
Aminoacyl-tRNA synthetases (aaRSs) play a key role in deciphering the genetic message by producing charged tRNAs and are equipped with proofreading mechanisms to ensure correct pairing of tRNAs with their cognate amino acid. Duplicated aaRSs are very frequent in Nature, with 25,913 cases observed in 26,837 genomes. The oligomeric nature of many aaRSs raises the question of how the functioning and oligomerization of duplicated enzymes is organized. We characterized this issue in a model prokaryotic organism that expresses two different threonyl-tRNA synthetases, responsible for Thr-tRNAThr synthesis: one accurate and constitutively expressed (T1) and another (T2) with impaired proofreading activity that also generates mischarged Ser-tRNAThr. Low zinc promotes dissociation of dimeric T1 into monomers deprived of aminoacylation activity and simultaneous induction of T2, which is active for aminoacylation under low zinc. T2 either forms homodimers or heterodimerizes with T1 subunits that provide essential proofreading activity in trans. These findings evidence that in organisms with duplicated genes, cells can orchestrate the assemblage of aaRSs oligomers that meet the necessities of the cell in each situation. We propose that controlled oligomerization of duplicated aaRSs is an adaptive mechanism that can potentially be expanded to the plethora of organisms with duplicated oligomeric aaRSs.