通过TENT4A和TENT4B的混合尾部保护mRNA免受快速死亡
Jaechul Lim1,2, Dongwan Kim1,2, Young-Suk Lee1,2
1Center for RNA Research, Institute for Basic Science, Seoul 151-742, Republic of Korea.
Science (New York, N.Y.)
|July 21, 2018
概括
研究人员确定TENT4A和TENT4B是化信使RNA (mRNA) 尾巴的酶. 这种化会产生混合的尾巴,保护mRNA免受降解,影响基因调节.
科学领域:
- 分子生物学
- 基因调控
- 生物化学
背景情况:
- RNA尾巴,特别是多A尾巴,对于调节信使RNA (mRNA) 的翻译和衰变至关重要.
- 最近发现的mRNA guanylation突出了对其酶的基础和功能意义的理解.
研究的目的:
- 确定负责mRNA化的酶.
- 阐明mRNA guanylation的机制和功能后果.
主要方法:
- 使用TENT4A (PAPD7) 和TENT4B (PAPD5) 进行蛋白质净化和酶分析.
- 分析mRNA尾部的组成和结构.
- 细胞耗尽研究以评估对mRNA稳定性和丰度的影响.
主要成果:
- 鉴定出TENT4A和TENT4B是催化mRNA guanylation的关键酶.
- 净化后的TENT4蛋白质会产生含有间歇性瓜诺辛残留物的混合多尾.
- 一个单一的瓜诺辛残留物有效抑制了CCR4-NOT死亡酶复合物.
- TENT4A/ TENT4B的耗尽会减少mRNA的半衰期和细胞丰度.
结论:
- TENT4A和TENT4B产生混合的多A尾部,通过防止快速死来使mRNA具有稳定性.
- 这种混合尾巴的机制代表了一种新的转录后基因调节层,扩大了已知的mRNA代谢的复杂性.
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