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人类TREM2的5'未翻译区域的翻译调节和蛋白质编码能力

Motoaki Yanaizu^1,2, Haruka Adachi¹, Makoto Araki³

¹Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi, Tokyo, 204-8588, Japan.

Communications biology

|June 8, 2023

概括

TREM2的5'非翻译区域 (UTR) 通过上游开始子 (uAUG) 调节其蛋白质翻译. 这种特定于人类和灵长类动物的机制影响TREM2表达及其在阿尔茨海默氏症等疾病中的作用.

科学领域:

分子生物学分子生物学
神经科学是一个神经科学.
细胞生物学细胞生物学

背景情况:

TREM2 (在骨髓细胞2表达的触发受体) 是一种转膜受体,对微质和巨细胞功能至关重要.
提高TREM2表达与与年龄相关的疾病有关,包括阿尔茨海默氏症 (AD),但其转化调节的理解不充分.
传递 RNA (mRNA) 的5'未翻译区域 (5'-UTR) 在控制蛋白质合成方面发挥着重要作用.

研究的目的:

研究人类TREM2的5'-UTR在调节其蛋白质翻译中的作用.
在TREM2 5'-UTR.中识别潜在的上游监管要素.
了解TREM2转化控制是如何受到细胞条件的影响,如氨基酸饥饿.

主要方法:

生物信息分析以确定TREM2 5'-UTR中的保存和物种特征.
报告员测定和西部抹杀,以评估具有5'-UTR和没有5'-UTR的结构体的TREM2蛋白表达.
位点定向的突变发生,以调查上游起始编码子 (uAUG) 的功能.
在氨基酸饥饿条件下进行蛋白质体降解测定和实验.

主要成果:

在人类TREM2的5'-UTR中发现了一种特定于物种的uAUG,而这种uAUG在许多其他物种中是不存在的.
通过UAUG,TREM2 5'-UTR抑制了正规TREM2蛋白 (dTREM2) 的翻译.
从uAUG启动的较短的TREM2异型 (uTREM2) 被检测到,但被发现被蛋白质体迅速降解.
在氨基酸饥饿期间,5'-UTR调节dTREM2表达的下调.

结论:

人类TREM2的5'-UTR在调节TREM2蛋白转化方面发挥着关键的,特定于物种的作用.
在5'-UTR中的uAUG充当了关键的调节元件,影响了正规TREM2表达和短,不稳定的异型的产生.
这种转化控制机制有助于TREM2表达水平,在神经退行性疾病和细胞应激反应的背景下可能是相关的.

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