Codon-specific effects of tRNA anticodon loop modifications on translational misreading errors in the yeast Saccharomyces cerevisiae.
Codon-specific effects of tRNA anticodon loop modifications on translational misreading errors in the yeast Saccharomyces cerevisiae.
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DOI：
10.1093/nar/gky664
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发表时间：
2018-11-02
影响因子：
14.9
通讯作者：
Farabaugh PJ
中科院分区：
文献类型：
--
作者：
Joshi K;Bhatt MJ;Farabaugh PJ
蛋白质合成需要高速度和准确性，以确保健康的细胞环境。在酿酒酵母菌蛋白质合成过程中，每个密码子的误差估计在10−3到10−4之间。在这里，我们发现酵母产生的错误可以变化100倍，从每个密码子10−6到10−4个错误。最常见的错误是近同源密码子GGA （Gly）在第二个位置的G•U不匹配。我们还表明，与我们之前的结果相反，酵母trna可以在摆动位置产生错误，包括不匹配，但效率很低。我们还评估了trna转录后修饰对误读频率的影响，这些修饰已知在酵母中调节同源密码子解码。我们测试了mcm5s2U34和t6A37的作用，并表明它们的作用取决于密码子反密码子相互作用的细节，包括与碱基错配相关的修饰位置和错配的性质。当误读GGA Gly密码子时，摆动尿苷的mcm5和s2修饰都能强烈稳定G2•U35错配，但对其他错配的影响较弱。相比之下，当误读UAA或UAG时，t6A37会使U1•U36失配不稳定，但会稳定第二和摆动位置的失配。
Protein synthesis requires both high speed and accuracy to ensure a healthy cellular environment. Estimates of errors during protein synthesis in Saccharomyces cerevisiae have varied from 10−3 to 10−4 errors per codon. Here, we show that errors made by in yeast can vary 100-fold, from 10−6 to 10−4 errors per codon. The most frequent errors require a G•U mismatch at the second position for the near cognate codon GGA (Gly). We also show, contrary to our previous results, that yeast tRNAs can make errors involving mismatches at the wobble position but with low efficiency. We have also assessed the effect on misreading frequency of post-transcriptional modifications of tRNAs, which are known to regulate cognate codon decoding in yeast. We tested the roles of mcm5s2U34 and t6A37 and show that their effects depend on details of the codon anticodon interaction including the position of the modification with respect to the base mismatch and the nature of that mismatch. Both mcm5 and s2 modification of wobble uridine strongly stabilizes G2•U35 mismatches when misreads the GGA Gly codon but has weaker effects on other mismatches. By contrast, t6A37 destabilizes U1•U36 mismatches when misreads UAA or UAG but stabilizes mismatches at the second and wobble positions.
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影响因子：
14.8
作者：
Gietz, R. Daniel;Schiestl, Robert H.
通讯作者：
Schiestl, Robert H.
影响因子：
14.9
作者：
Blanchet S;Cornu D;Argentini M;Namy O
通讯作者：
Namy O
影响因子：
5.6
作者：
HIRSH
通讯作者：
HIRSH
影响因子：
5.6
作者：
Hagervall, TG;Pomerantz, SC;McCloskey, JA
通讯作者：
McCloskey, JA
影响因子：
5.3
作者：
Johansson, Marcus J. O.;Esberg, Anders;Bystrom, Anders S.
通讯作者：
Bystrom, Anders S.