5' UTR 关键调控逻辑控制了对正规RNA和非编码RNA的核糖体参与
Siang Chen1, Dongdong Zhang1, Hao Wang1
1Institute of Biophysics Chinese Academy of Sciences.
概括
核糖体与RNA的接触是由5'未翻译区域 (UTR) 的特征决定的. 这项研究揭示了序列特征,而不是编码潜力,决定了核糖体与信使RNA (mRNA) 和非编码RNA (ncRNA) 结合.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物信息学是一种生物信息学.
背景情况:
- 细胞的翻译启动是由5'未翻译区域 (UTR) 的元素调节的,例如上游开放的读取框架 (uORF),Kozak序列和二次结构,影响着核糖体动力学.
- 核糖体造型和组学表明核糖体与非编码RNA (ncRNA) 相互作用,并翻译短开放读取 (sORF),挑战了对蛋白质合成的正规mRNA中心观点.
研究的目的:
- 系统地分析5' UTR架构跨规范mRNA,翻译活跃的核糖体关联ncRNA和非翻译的ncRNA.
- 开发和验证基于5' UTR特征的翻译效率预测模型.
- 调查与ncRNAs的核糖体参与的进化和机制基础.
主要方法:
- 在精心策划的人类数据集中对5' UTR序列和特征进行系统分析,将转录分类为正规mRNA,核糖体相关的ncRNA和非翻译的ncRNA.
- 开发一个随机森林模型,plusCE,整合5' UTR特征来预测翻译效率.
- 跨RNA类别的转化特征 (5' UTR长度,uORF计数) 和进化特征的比较分析.
主要成果:
- 规范的mRNA具有最佳的翻译特征 (短的5'UTR,少的uORF),而翻译的ncRNA表现出中间特征,而非翻译的ncRNA表现出最弱的特征.
- 在mRNA中较长的5' UTRs通过保存的调节元素保持高的翻译效率.
- plusCE模型准确地预测了翻译效率,优于现有方法,并突出了5' UTR序列特征在核糖体参与中的作用.
结论:
- 核糖体与RNA转录的参与主要是由5' UTR序列特征决定的,为翻译控制建立了监管语法.
- 核糖体结合的ncRNA缺乏编码相关的进化特征,这表明它们通过允许序列特征而不是通过进化的编码功能来参与翻译机制.
- 这些发现强调了5' UTR序列架构在调制翻译中的重要性,并为设计调节元件以控制蛋白质合成提供了见解.
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