近年來,，合成生物學(xué)發(fā)展迅速,，研究人員給微生物設(shè)計的功能也越來越復(fù)雜,，但在細胞行為的可預(yù)測性、安全性和高效性方面仍有很多難以解決的問題,。據(jù)每日科學(xué)網(wǎng)站5月30日（北京時間）報道,，美國能源部勞倫斯伯克利國家實驗室生物學(xué)家創(chuàng)造出一種能放大RNA（核糖核酸）轉(zhuǎn)錄信號的變體，可大大簡化控制細胞行為的生物線路,，并將改變未來基因網(wǎng)絡(luò)的設(shè)計與構(gòu)建,，使控制細胞行為在安全高效性上更進一步。研究論文發(fā)表在最近出版的美國《國家科學(xué)院院刊》（PNAS）上,。
合成生物學(xué)有兩個基本目標,，一是給標準化的基因制造相似的親屬家族，二是編程控制細胞行為,，提高細胞行為的可預(yù)測性,。細胞行為通常由多個不同的基因通過RNA機制來共同調(diào)控，合成生物學(xué)家正是利用RNA調(diào)控機制來編寫細胞的基因網(wǎng)絡(luò)程序,，以達到某種特殊目的,。但迄今為止，各種編程都需要增加蛋白質(zhì)以放大RNA的調(diào)控信號,，這些蛋白質(zhì)增加了生物路線的復(fù)雜性,。早期開發(fā)的大部分技術(shù)也因此在實驗中效率很低且出現(xiàn)大量失誤。
研究人員亞當·阿金和同事不用增加蛋白質(zhì),，直接放大了RNA分子的調(diào)控信號,。他們利用金黃色葡萄球菌細胞質(zhì)粒pT181中的一種基本元素,，制造出了一種衰減子的變體,。該變體能在同一個細胞中獨立調(diào)控多靶點的轉(zhuǎn)錄行為，但其功能與RNA媒介轉(zhuǎn)錄衰減機制相反,，并通過RNA間的相互作用來執(zhí)行調(diào)控基因活性和轉(zhuǎn)錄的功能,。研究人員隨后在最普通的埃希氏菌屬大腸桿菌（Escherichia coli）中驗證了其功能。
阿金說：“這種變體只是對天然RNA轉(zhuǎn)錄衰減子的結(jié)構(gòu)做了微小的正交改變而成,，但其獨立控制轉(zhuǎn)錄過程就比基因網(wǎng)絡(luò)所需遵循的構(gòu)建規(guī)則更簡單,。”之前的其他RNA調(diào)控機制，需要一個網(wǎng)絡(luò)協(xié)同合作多條線路,，每個基因只能執(zhí)行整個控制功能中的部分任務(wù),，而他們制造的衰減子變體簡化了路線，能一次完成整個控制功能,。
阿金還指出,，這種利用自然界RNA系統(tǒng)構(gòu)造正交變體的策略也能用于其他基因調(diào)控機制，為RNA轉(zhuǎn)錄調(diào)控提供了多種功能的新設(shè)計,。他們利用RNA調(diào)控系統(tǒng)開發(fā)出一個完整且能升級的生物工程系統(tǒng),，最終制造出一種整合了主體線路設(shè)計與部署實施的革新型工具,。（生物谷Bioon.com）
生物谷推薦原文出處：
Proceedings of the National Academy of Sciences DOI： 10.1073/pnas.1015741108
Versatile RNA-sensing transcriptional regulators for engineering genetic networks
Lucks, Julius B.; Qi, Lei; Mutalik, Vivek K.; Wang, Denise; Arkin, Adam P.
The widespread natural ability of RNA to sense small molecules and regulate genes has become an important tool for syntheticbiology in applications as diverse as environmental sensing and metabolic engineering. Previous work in RNA synthetic biologyhas engineered RNA mechanisms that independently regulate multiple targets and integrate regulatory signals. However, intracellularregulatory networks built with these systems have required proteins to propagate regulatory signals. In this work, we removethis requirement and expand the RNA synthetic biology toolkit by engineering three unique features of the plasmid pT181 antisense-RNA-mediatedtranscription attenuation mechanism. First, because the antisense RNA mechanism relies on RNA-RNA interactions, we show howthe specificity of the natural system can be engineered to create variants that independently regulate multiple targets inthe same cell. Second, because the pT181 mechanism controls transcription, we show how independently acting variants can beconfigured in tandem to integrate regulatory signals and perform genetic logic. Finally, because both the input and outputof the attenuator is RNA, we show how these variants can be configured to directly propagate RNA regulatory signals by constructingan RNA-meditated transcriptional cascade. The combination of these three features within a single RNA-based regulatory mechanismhas the potential to simplify the design and construction of genetic networks by directly propagating signals as RNA molecules.
