内部核糖体进入点增强转化在反意义非编码SINEUP和循环RNA中
Sabrina D'Agostino1, Abraham Tettey-Matey2, Massimiliano Volpe1
1Center for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Nucleic acids research
|August 18, 2025
概括
内部核糖体进入点 (IRES) 可以驱动翻译. 这项研究表明,IRES也可以增强转基因中其他mRNA的翻译,作为基因表达的新型调节机制.
科学领域:
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
- 基因表达规范 基因表达规范
背景情况:
- 内部核糖体进入点 (IRES) 是mRNA的5'-未翻译区域中的RNA序列,它们启动了独立于帽子的翻译.
- IRES驱动下游蛋白质编码开放阅读框架的 cis 作用翻译.
- IRES元素的精确机制和更广泛的功能仍在调查中.
研究的目的:
- 调查IRES序列中介跨作用翻译的潜力.
- 探索SINEUPs (反意义长非编码RNA) 在调节基因表达中的功能.
- 为了确定新的跨作用IRES元素,包括循环RNA.
主要方法:
- 在cis和trans中对IRES活动的功能性表征.
- 人工SINEUP结构的设计和合成.
- 使用分子生物学技术识别和验证具有跨作用IRES活性的自然非编码RNA.
主要成果:
- 证明IRES序列可以通过反意义相互作用来诱导独立的mRNA的跨作用翻译.
- 确定已知的病毒和细胞IRES序列可以在合成SINEUP中充当效应器域.
- 鉴定了一种循环RNA (circMyc),通过作为一种反意义IRES来增强转基因中的蛋白质表达.
结论:
- SINEUPs作为交换作用的IRES运作,利用效应器和约束域进行交换控制.
- 某些循环RNA,如circMyc,可以充当跨作用IRES,扩大翻译调节器的范围.
- 这些发现揭示了在转化层面调节基因表达的新机制.
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