tRNA methylation resolves codon usage bias at the limit of cell viability.
tRNA methylation resolves codon usage bias at the limit of cell viability.
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DOI：
10.1016/j.celrep.2022.111539
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发表时间：
2022-10-25
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
每个基因组的密码子使用与tRNA异源受体的丰度密切相关。密码子使用偏好如何通过tRNA转录后修饰来解决在很大程度上是未知的。在这里，我们证明了反密码子3′侧37位鸟苷（m1G37）的N1甲基化，虽然不直接负责密码子的阅读，但却是解决脯氨酸密码子差异解码的中和剂。缺乏m1G37的无活力大肠杆菌菌株的全基因组抑制剂筛选鉴定了proS抑制剂突变，表明甲基化与tRNA脯氨酰氨酰化的偶联限制了细胞活力。使用这些抑制剂，其中脯氨酰氨酰化是从tRNA甲基化解耦，我们表明，m1G37中和脯氨酸密码子的差异翻译的主要isoacceptor。缺乏m1G37使这种中和失活，并暴露了对细胞活力的次要同种受体的需要。这项工作对专门使用主要同种受体生存的细菌物种具有医学意义。增田等人发现，从tRNA反密码子的3′端缺失m1G37，使得反密码子的修饰的摆动核苷酸不足以解码一组稀有密码子，从而为tRNA反密码子的37位和摆动位置之间的“修饰回路”提供了功能基础。
Codon usage of each genome is closely correlated with the abundance of tRNA isoacceptors. How codon usage bias is resolved by tRNA post-transcriptional modifications is largely unknown. Here we demonstrate that the N1-methylation of guanosine at position 37 (m1G37) on the 3′-side of the anticodon, while not directly responsible for reading of codons, is a neutralizer that resolves differential decoding of proline codons. A genome-wide suppressor screen of a non-viable Escherichia coli strain, lacking m1G37, identifies proS suppressor mutations, indicating a coupling of methylation with tRNA prolyl-aminoacylation that sets the limit of cell viability. Using these suppressors, where prolyl-aminoacylation is decoupled from tRNA methylation, we show that m1G37 neutralizes differential translation of proline codons by the major isoacceptor. Lack of m1G37 inactivates this neutralization and exposes the need for a minor isoacceptor for cell viability. This work has medical implications for bacterial species that exclusively use the major isoacceptor for survival. Masuda et al. show that loss of m1G37 from the 3′ side of the tRNA anticodon renders a modified wobble nucleotide of the anticodon insufficient to decode a set of rare codons, providing a functional underpinning for the “modification circuit” between position 37 and the wobble position of the tRNA anticodon.
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影响因子：
16.8
作者：
Christian T;Sakaguchi R;Perlinska AP;Lahoud G;Ito T;Taylor EA;Yokoyama S;Sulkowska JI;Hou YM
通讯作者：
Hou YM
影响因子：
14.9
作者：
Chan PP;Lowe TM
通讯作者：
Lowe TM
影响因子：
5.6
作者：
Christian T;Lahoud G;Liu C;Hou YM
通讯作者：
Hou YM
DOI：
10.1128/genomea.01038-14
发表时间：
2014-10-16
期刊：
Genome announcements
影响因子：
--
作者：
Grenier F;Matteau D;Baby V;Rodrigue S
通讯作者：
Rodrigue S
DOI：
10.1007/bf00330047
发表时间：
1982-01-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
BYSTROM, AS;BJORK, GR
通讯作者：
BJORK, GR