人工小RNA调控元件在合成生物学中的应用

Application of synthetic small regulatory RNAs in synthetic biology

摘要:

合成生物学通过改造天然系统或创造生物元件、模块和系统赋予生命体新的功能,为农业、能源、制造业及医学进步带来了巨大推动力。对元件、模块或系统的精准、定量及高效调控将对合成生命系统的控制至关重要。细菌小RNA是一类长度在50–300 bp且通常不具备翻译能力的功能小分子,在环境胁迫响应、代谢变化适应和细菌毒力控制过程中发挥着不可替代的调控作用。近年来,基于天然小RNA设计构建的人工小RNA调控元件的工作日益丰富,实现了对目的基因甚至通路的有效抑制或激活。人工小RNA分子小、灵活性高,可程序化且易于设计,几乎不会对宿主细胞造成代谢负担,因此在合成生物学中具备广泛应用前景。为促进对人工小RNA的机理理解及应用拓展,本文围绕若干人工小RNA调控元件进行了系统介绍及比较;此外,总结了其在合成生物学中的代表性应用;最后,对其未来优化方向进行了讨论。

关键词:非编码;人工小RNA;基因抑制;基因激活;智能调控

Abstract:

Synthetic biology has brought enormous impacts to the advancement of agriculture, energy,manufacturing and medicine by redesigning existing natural systems or creating biological elements,modules and systems to endow life with new functions. The precise, quantitative and efficient regulation of biological elements, modules and systems is critical for controlling living systems. Bacterial small regulatory RNAs are a class of functional molecules with a length of 50–300 nt and usually do not translate into proteins. They play an irreplaceable role in environmental stress response, metabolic adaptation and bacterial virulence control. In recent years, synthetic small regulatory RNAs have been designed based on natural small RNAs and were used to effectively inhibit or activate target genes and even pathways. Synthetic small regulatory RNAs have broad application advantages in synthetic biology because of their small size, high flexibility, programmability, easy design and little metabolic burden on host cells. To better understand the synthetic small regulatory RNAs and promote its application, this review summarized several synthetic small RNA systems and their representative applications in synthetic biology. Finally, future optimization directions were prospected.

Key words:noncoding;synthetic small RNAs;gene inhibition;gene activation;intelligent regulation