A tRNA t6A modification system contributes to the sensitivity towards the toxin β-N-methylamino-L-alanine (BMAA) in the cyanobacterium Anabaena sp. PCC 7120.
A tRNA t6A modification system contributes to the sensitivity towards the toxin β-N-methylamino-L-alanine (BMAA) in the cyanobacterium Anabaena sp. PCC 7120.
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DOI：
10.1016/j.aquatox.2022.106121
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发表时间：
2022-02
影响因子：
4.5
通讯作者：
Zi-Qian Wang;Cheng‐Cai Zhang
中科院分区：
文献类型：
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作者：
Zi-Qian Wang;Cheng‐Cai Zhang
蓝藻是放氧的光合自养生物，对环境中的营养循环是必不可少的。它们拥有多种控制细胞活动的机制，以适应环境。虽然蛋白质翻译对于细胞的生存和适应是必不可少的，但蓝藻对这一过程的调节和灵活性知之甚少。β-N-甲氨基-L-丙氨酸(BMAA)是一种环境神经毒素，对丝状重氮蓝藻AnabaenaPCC7120有较强的毒性。在本研究中，通过对BMAA抗性突变体的遗传分析，我们证明了负责用N(6)-苏氨酰氨基甲酰腺苷(T6A)修饰ANN解码tRNAs的系统通过翻译控制参与了BMAA的敏感性。BMAA和t6A生物合成途径的失活都影响翻译保真度和核糖体组装。然而，这两个因素要么在翻译延长上表现出相加的作用，要么在翻译保真度上相互减弱，或者对抑制翻译过程不同步骤的抗生素的耐药性/敏感性相互减弱。BMAA对翻译和转录有广泛的影响，一旦BMAA进入细胞，t6A生物合成途径的存在就增加了细胞对这种毒素的敏感性。筛选BMAA抗性突变体是深入了解BMAA毒性机制的有效方法。此外，BMAA是探索蓝藻翻译灵活性的有用工具，相应抗性突变体的特征将有助于我们揭示蓝藻适应不断变化的环境的翻译机制。
Cyanobacteria are oxygen-evolving photosynthetic autotrophs essential for nutrient cycling in the environment. They possess multiple control mechanisms for their cellular activities in order to adapt to the environment. While protein translation is essential for cell survival and adaptation, the regulation and the flexibility of this process are poorly understood in cyanobacteria. β-N-methylamino-L-alanine (BMAA), an amino acid analog proposed as an environmental neurotoxin, is highly toxic to the filamentous diazotrophic cyanobacteriumAnabaenaPCC 7120. In this study, through genetic analysis of BMAA-resistant mutants, we demonstrate that the system responsible for modification of ANN-decoding tRNAs with N(6)-threonylcarbamoyl adenosine (t6A) is involved in BMAA sensitivity through the control of translation. Both BMAA and inactivation of the t6A biosynthesis pathway affect translational fidelity and ribosome assembly. However, the two factors display either additive effects on translational elongation, or attenuate each other over translational fidelity or the resistance/sensitivity to antibiotics that inhibit different steps of the translational process. BMAA has a broad effect on translation and transcription, and once BMAA enters the cells, the presence of the t6A biosynthesis pathway increases the sensitivity of the cells towards this toxin. BMAA-resistant mutants screening is an effective method for getting insight into the toxic mechanisms of BMAA. In addition, BMAA is a useful tool for probing translational flexibility of cyanobacteria, and the characterization of the corresponding resistant mutants should help us to reveal translational mechanism allowing cyanobacteria to adapt to changing environments.