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在逆转录过程中因诺辛诱导的基配对多样性

Ya Ying Zheng^1,2, Kaalak Reddy², Sweta Vangaveti²

¹Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, New York 12222, United States.

ACS chemical biology

|January 22, 2024

概括

氨酸到氨酸 (A-to-I) 的RNA编辑,特别是超编辑,会影响逆转录酶 (RT) 活性和测序精度. 这项研究揭示了因诺辛修饰如何影响RT解码,并提供了对HIV-1RT相互作用的结构性见解.

科学领域:

生物化学生物化学
分子生物学分子生物学
病毒学病毒学

背景情况:

氨酸对氨酸 (A-to-I) 编辑对于细胞功能和RNA病毒感染性至关重要.
素修饰可以改变病毒RNA复制和细胞转录组,类似于A-G过渡.
超编辑对病毒聚合酶活性和测序忠实性的影响尚不清楚.

研究的目的:

研究因诺辛修饰数和位置对逆转录酶 (RT) 解码结果的影响.
阐明HIV-1RT中氨酸适应的结构基础及其对基配对的影响.
了解超编辑如何影响RNA测序和转录.

主要方法:

系统地探索使用三种不同的RT和桑格测序对解码的氨酸修饰效应.
对HIV-1 RT进行分子动力学模拟,以分析氨酸适应和基配对.
改变RNA基质中因诺辛的数量和位置.

主要成果:

单独或集成的异素修饰会对RT活性产生不同的影响.
分子动力学模拟显示,蛋白质-核酸相互作用是理解HIV-1RT中氨酸基配对的关键.
桑格测序结果可以在逆转录过程中通过超变异的因诺辛重塑.

结论:

伊诺辛超编辑显著影响RT忠实性和解码,可能改变RNA测序结果.
对HIV-1RT-氨酸相互作用的结构见解对于理解A-to-I编辑的生理意义至关重要.
这项工作奠定了解密超编辑因诺辛在细胞和病毒RNA转录中的作用的基础.

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