通过功能上相互依赖的活动在一个地点进行编辑和甲基化
Mary Anne T Rubio1, Kirk W Gaston1,2, Katherine M McKenney1
1Department of Microbiology, Ohio State Biochemistry Program and The Center for RNA Biology, The Ohio State University, Columbus, Ohio 43210, USA.
Nature
|February 24, 2017
概括
核酸中的化学变化至关重要,但常常不被充分理解. 这项研究揭示了细胞因子甲基化是Trypanosoma brucei tRNA脱胺的先决条件,解释了基因组的稳定性.
科学领域:
- 分子生物学
- 生物化学
- 遗传学
背景情况:
- 核酸具有100多种已知的化学修饰,影响和糖.
- 大多数核酸修饰的生物合成途径在很大程度上仍未被阐明.
- 在体外溶解酶具有挑战性,这表明复杂的修饰途径或相互依赖.
研究的目的:
- 在真核生物中研究tRNA细胞因子转化为尿素的机制.
- 阐明修饰相互依赖在酶活性中的作用.
- 了解Trypanosoma brucei如何保持基因组完整性,尽管它具有突变性去氨基酶.
主要方法:
- 在Trypanosoma brucei tRNAThr中研究了细胞素32的修饰.
- 使用纯化的成分,包括TRM140甲基转移酶和ADAT2/3脱氨酶,在体内复制酶活性.
- 甲基转移酶和脱氨酶的同时表达,以评估酶活性和突变性.
主要成果:
- 在T. brucei中,细胞因子32被TRM140甲基化为3-甲基细胞因子 (m3C).
- m3C是通过ADAT2/3对3-甲基尤里丁 (m3U) 的后续除氨的先决条件.
- 同时表达TRM140和ADAT2/ 3抑制ADAT2/ 3的突变性,保持基因组的稳定性.
结论:
- 一个修改相互依赖的模型被证明,其中甲基化先于去胺.
- 这种序列性修饰途径解释了T. brucei缺乏批发性除.
- 这些发现提供了对突变性脱氨酶,包括人类AID的调节的见解.
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