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Nat Biotechnol:科学家首次实现活细胞RNA标记与无背景成像

2019-11-07 佚名 中国科学报

它显示了利用荧光RNA可对单细胞中mRNA的翻译过程进行定量研究。癌细胞中mRNA水平与其编码蛋白质水平之间存在较低相关性,提示癌细胞的翻译调控显着失调,这为癌症的诊疗提供一种全新的思路。

它显示了利用荧光RNA可对单细胞中mRNA的翻译过程进行定量研究。癌细胞中mRNA水平与其编码蛋白质水平之间存在较低相关性,提示癌细胞的翻译调控显着失调,这为癌症的诊疗提供一种全新的思路。

华东理工大学生物反应器工程国家重点实验室的杨弋、朱麟勇等教授历经7年合作研究,在荧光RNA及活细胞RNA成像领域获突破性进展。他们原创的系列高性能荧光RNA,在国际上首次实现了不同种类RNA在动物细胞内的荧光标记与无背景成像。11月5日,该成果以封面论文形式发表于《自然—生物技术》。

荧光蛋白标记技术是蛋白质研究的巨大助力,其研究在2008年曾获得诺贝尔奖。类似的,RNA研究也迫切需要这样的颠覆性研究工具。但迄今为止,在自然界尚未发现天然存在的荧光RNA;而科学家们几经努力人工合成的少数几种荧光RNA又性能过低,难以实用。针对这一亟需解决的技术挑战,杨弋、朱麟勇等组成了化学生物学与合成生物学联合交叉攻关团队,通过全新的分子设计及分子共同定向进化思路,首次获得了系列高亮、稳定、低背景的荧光RNA。

这些荧光RNA结构紧凑,特异结合创新染料分子后产生强烈荧光,可具有蓝、绿、黄、橙、红等不同颜色,与五颜六色的辣椒相似,因此被命名为Pepper。它们可通过基因编辑等手段插入到不同RNA分子序列中,在活细胞内对这些分子进行荧光标记和实时、超分辨成像,却不影响它们的转录、定位、翻译、降解等正常活动。由于荧光RNA标记可逆,因此它们在细胞内的颜色可随意改变,这种灵活性对于荧光标记稳定细胞株和转基因动物的构建十分有利。

与现有技术相比,我国原创的荧光RNA在亲和力、稳定性、信噪比、活细胞荧光亮度等方面提升了1到3个数量级,体现了荧光RNA从概念到实用的突破,为活细胞中RNA的功能研究提供了极具价值的工具。除了作为RNA标记工具外,研究人员表示它们还有望在活细胞代谢物检测技术、核酸即时监测技术、单分子多重检测技术等前沿领域实现二次颠覆,为生命科学研究与医学即时诊断甚至实时诊断技术的发展提供新的机遇。

原始出处:
Chen X1,2,3, Zhang D1,4, Su N1,3, et al.Visualizing RNA dynamics in live cells with bright and stable fluorescent RNAs.Nat Biotechnol. 2019 Nov;37(11):1287-1293. doi: 10.1038/s41587-019-0249-1. Epub 2019 Sep 23.

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    2020-02-01 cathymary
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    2020-08-31 liye789132251
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    2019-11-23 sunylz
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    2020-02-05 shock_melon

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