微RNA减缓翻译核糖体的速度,以防止蛋白质在真核生物中错误折叠
Hiroaki Sako1, Mohieldin Youssef1, Olga Elisseeva1
1Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Okinawa, Japan.
The EMBO journal
|July 26, 2023
概括
微RNAs (miRNAs) 阻碍了核糖体翻译,防止了真核细胞中的蛋白质错误折叠. 这种特定于真核生物的机制有助于适当的蛋白质折叠,并为错误折叠疾病提供新的治疗点.
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:
- 已知较慢的翻译速率可以通过允许适当折叠的时间来减少蛋白质错折.
- 非最佳的编码子介导翻译速度的减少,这是从细菌到人类的保存机制.
- 对于共翻译折叠的真核生物特异性机制在很大程度上是未知的.
研究的目的:
- 调查微RNA (miRNA) 是否代表共翻译蛋白折叠的真核生物特异性机制.
- 了解为什么miRNAs结合编码序列 (CDS),尽管抑制效率低.
主要方法:
- 对核糖体概况和miRNA结合部位的分析,以检测核糖体停滞.
- 评估对全球或特定miRNA缺陷的蛋白质聚合.
- 使用非分裂的shRNA (miRNA模仿) 来减缓核糖体的救援实验.
主要成果:
- 微RNAs (miRNAs) 已被证明可以暂时阻断翻译核糖体,防止蛋白质错误折叠,对蛋白质丰度的影响最小.
- miRNA缺乏加速了核糖体的速度,并诱导了易发生错折的多的聚合.
- 不分裂的shRNAs通过减缓核糖体来挽救miRNA缺乏引起的缺陷.
- 与II型糖尿病相关的前胰岛素错误折叠,通过使用非分裂的shRNAs来解决.
结论:
- 微RNAs (miRNAs) 提供了一个真核生物特异性机制,通过阻断核糖体来共同翻译蛋白质折叠.
- 这项研究揭示了针对蛋白质错折疾病的新型作用机制.
- 这些发现表明,对于涉及蛋白质错折的II型糖尿病等疾病的潜在治疗策略.
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