RNA m6A Modification Alteration by Black Phosphorus Quantum Dots Regulates Cell Ferroptosis: Implications for Nanotoxicological Assessment,Small Methods

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RNA m6A Modification Alteration by Black Phosphorus Quantum Dots Regulates Cell Ferroptosis: Implications for Nanotoxicological Assessment
Small Methods ( IF 10.7 ) Pub Date : 2021-01-18 , DOI: 10.1002/smtd.202001045
Fengkai Ruan ₁ , Jie Zeng ₁ , Hanying Yin ₁ , Shengwei Jiang ₂ , Xisen Cao ₁ , Naying Zheng ₁ , Changshun Han ₁ , Chuchu Zhang ₁ , Zhenghong Zuo ₁ , Chengyong He ₁

Affiliation

Nanosafety is a major concern for nanotechnology development. Evaluation of the transcriptome and the DNA methylome is proposed for nanosafety assessments. RNA m6A modification plays a crucial role in development, disease, and cell fate determination through regulating RNA stability and decay. Here, since black phosphorus quantum dots (BPQDs), among many other types of QDs, increase the global m6A level and decrease the demethylase ALKBH5 level in lung cells, the epitranscriptome is taken into consideration for the first time to evaluate nanosafety. Both the transcriptome and m6A epitranscriptome analyses show that BPQDs alter many biological processes, such as the response to selenium ions and the lipoxygenase pathway, indicating possible ferroptosis activation. The results further show that BPQDs cause lipid peroxidation, mitochondrial dysfunction, and iron overload. Recognition of these modified mRNAs by YTHDF2 leads to mRNAs’ decay and eventually ferroptosis. This study shows that RNA m6A modification not only is a more sophisticated indicator for nanosafety assessment but also provides novel insight into the role of RNA m6A in regulating BPQD‐induced ferroptosis, which may be broadly applicable to understanding the functions of RNA m6A under stress.

中文翻译：

黑磷量子点的 RNA m6A 修饰改变调节细胞铁死亡：对纳米毒理学评估的意义

纳米安全是纳米技术发展的一个主要问题。建议对转录组和 DNA 甲基化组进行评估以进行纳米安全评估。RNA m6A 修饰通过调节 RNA 稳定性和衰变在发育、疾病和细胞命运决定中起着至关重要的作用。在这里，由于黑磷量子点（BPQDs）在许多其他类型的量子点中，增加了肺细胞中的全局m6A水平并降低了去甲基化酶ALKBH5水平，因此首次考虑表观转录组来评估纳米安全性。转录组和 m6A 表观转录组分析均表明 BPQD 改变了许多生物过程，例如对硒离子和脂氧合酶途径的反应，表明可能存在铁死亡激活。结果进一步表明 BPQDs 引起脂质过氧化，线粒体功能障碍和铁过载。YTHDF2 识别这些修饰的 mRNA 会导致 mRNA 衰变并最终导致铁死亡。这项研究表明，RNA m6A 修饰不仅是一个更复杂的纳米安全评估指标，而且还为 RNA m6A 在调节 BPQD 诱导的铁死亡中的作用提供了新的见解，这可能广泛适用于理解 RNA m6A 在压力下的功能。

更新日期：2021-03-15

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