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转化依赖和转化独立的mRNA衰变通过在T细胞激活过程中由核糖体密度定义的相互排斥的途径发生

Blandine C Mercier¹, Emmanuel Labaronne^2,3, David Cluet²

¹RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

Genome research

|March 20, 2024

概括

大多数细胞转录通过转化依赖mRNA衰变 (TDD) 降解. 未翻译区域长度,核糖体密度和密码子含量影响TDD,TDD随着T细胞激活而动态变化.

科学领域:

分子生物学分子生物学
细胞生物学细胞生物学
免疫学免疫学免疫学

背景情况:

mRNA翻译和衰变是关键的,相互连接的细胞过程.
同转移的mRNA降解会影响mRNA循环,但转化依赖的mRNA衰变 (TDD) 和转化独立的mRNA衰变 (TID) 的作用尚未完全理解.

研究的目的:

在小鼠初级CD4+T细胞中全面分析基底和信号诱导的TDD和TID.
确定决定TDD大小的因素以及这些关系在T细胞激活时如何变化.

主要方法:

在小鼠初级CD4+T细胞中分析mRNA衰变途径.
研究了未翻译区域长度,核糖体密度和编码子含量 (GC3) 对TDD的影响.
在T细胞激活后检查了TDD及其决定因素的动态变化.

主要成果:

大多数细胞转录表现出一定程度的转化依赖衰变.
未翻译区域的长度,核糖体密度和GC3含量是TDD的关键决定因素.
T细胞激活动态地改变了编码子含量和TDD之间的关系,包括扭转GC3/AU3编码子效应.

结论:

在哺乳动物细胞中,mRNA翻译和衰变之间存在着强烈的动态相互作用.
TDD是mRNA周转的重要贡献者,受转录特征和细胞激活状态的影响.

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