人类SAMD9是一种可激活的抗子核酶,可以抑制子特异性蛋白质合成
Fushun Zhang1, Quanquan Ji2, Juhi Chaturvedi3
1Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Science advances
|June 7, 2023
概括
人类SAMD9作为一个抗核酶 (ACNase),分裂氨酸tRNA (tRNAPhe) 来阻止蛋白质合成. 这种新发现的ACNase在抗病毒防御和人类疾病中起作用.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 人类遗传学 人类遗传学
背景情况:
- 微生物抗核酶 (ACNases) 耗尽tRNA,以抑制蛋白质合成作为一种防御机制.
- 这种tRNA枯竭策略在多细胞真核生物中以前没有被观察到.
研究的目的:
- 研究人类SAMD9的功能及其作为ACNase的潜在作用.
- 阐明SAMD9-介导tRNA分裂的机制及其生物学意义.
主要方法:
- 生物化学测试以评估SAMD9的核酶活性.
- 确定SAMD9的基质特异性及其作用的结构基础.
- 通过病毒感染和与疾病相关的突变对SAMD9激活的分析.
主要成果:
- 人类SAMD9的功能是ACNase,特别是分裂氨酸tRNA (tRNAPhe).
- SAMD9的激活发生在波克斯病毒感染期间,并通过与人类疾病相关的突变.
- 基质特异性是由真核tRNAPhe的独特修饰决定的,使其易受SAMD9.
结论:
- 在人体中,SAMD9介导的tRNAPhe枯竭代表了一种抗病毒机制.
- 失调的SAMD9活性有助于引起与人类疾病相关的致病性疾病.
- 与微生物对应物相比,SAMD9 ACNase代表了一个独特的,可能是融合进化的免疫防御策略.
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