伪氨基酸分析揭示了酵母和人体细胞中受调节的mRNA伪氨基化
Thomas M Carlile1, Maria F Rojas-Duran1, Boris Zinshteyn1
1Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature
|September 6, 2014
概括
伪乌里丁是一种关键的RNA修饰物,最近在酵母和人类的信使RNA (mRNA) 中发现. 这一发现揭示了细胞如何快速改变基因表达以应对环境变化.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 伪尤里丁是最丰富的RNA修饰,主要存在于tRNA和rRNA等非编码RNA中.
- 它稳定了RNA结构并增强了RNA功能.
- 在信使RNA (mRNA) 中自然存在的伪尿氨酸以前没有被描述,因此其生理相关性尚不清楚.
研究的目的:
- 为了全面分析跨Saccharomyces cerevisiae和人类RNA的伪化.
- 为了识别新的伪化位点,特别是在mRNA中.
- 研究负责mRNA伪尿和其调节的酶.
主要方法:
- 开发和应用Pseudo-seq,一种全基因组,单核酸分辨率方法用于伪尿素识别.
- 在酵母和人类RNA中进行全基因组的伪尿基化分析.
- 基因分析用于将修改位点分配给特定的伪尿素合成酶.
主要成果:
- 伪seq在非编码RNA中确定了众多已知和新型伪乌里丁位点.
- 在mRNA中发现了数百个伪尿化位点.
- 大多数新型伪乌里丁位点归因于七个保存的伪乌里丁合成酶 (Pus1-4,6,7,9).
- mRNA伪尿化受到环境信号 (例如,营养素/血清饥饿) 的显著调节.
结论:
- 伪化发生在自然存在的mRNA中,挑战了以前的假设.
- 可诱导的mRNA伪化提供了一个快速,规范的基因代码变化的机制.
- 这项研究揭示了伪尿化作用的新作用,并确定了与人类疾病相关的伪尿合成酶的标.
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