合成生物学 ›› 2023, Vol. 4 ›› Issue (1): 141-164.DOI: 10.12211/2096-8280.2022-050

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RNA转录后代谢时空精密控制技术

刘韧玫1,2,3, 李乐诗1,2, 杨小燕1,2, 陈显军1,2, 杨弋1,2   

  1. 1.华东理工大学光遗传学与合成生物学交叉学科研究中心,生物反应器工程国家重点实验室,上海 200237
    2.华东理工大学药学院,上海市细胞代谢光遗传学技术前沿科学研究基地,上海 200237
    3.华东理工大学生物工程学院,上海 200237
  • 收稿日期:2022-09-13 修回日期:2022-11-18 出版日期:2023-02-28 发布日期:2023-03-07
  • 通讯作者: 杨弋
  • 作者简介:刘韧玫(1989—),女,博士,讲师。研究方向为光遗传学与合成生物学(细胞代谢监测与控制技术)。E-mail:renmei2018@ecust.edu.cn
    杨弋(1973—),男,教授,博士生导师。研究方向为控制与监测细胞内分子过程的合成生物技术与光遗传学前沿技术、癌症及代谢类疾病药理及药物筛选技术、蛋白质特异性标记与翻译后修饰的鉴定、细胞内原位成像、蛋白质药物生产技术等。E-mail:yiyang@ecust.edu.cn
    第一联系人:刘韧玫(1989—),女,博士,讲师。研究方向为光遗传学与合成生物学(细胞代谢监测与控制技术)。
  • 基金资助:
    国家重点研发计划(2022YFC3400100);国家自然科学基金(32121005)

Technologies for precise spatiotemporal control of post-transcriptional RNA metabolism

Renmei LIU1,2,3, Leshi LI1,2, Xiaoyan YANG1,2, Xianjun CHEN1,2, Yi YANG1,2   

  1. 1.Optogenetics & Synthetic Biology Interdisciplinary Research Center,State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China
    2.Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China
    3.School of Bioengineering,East China University of Science and Technology,Shanghai 200237,China
  • Received:2022-09-13 Revised:2022-11-18 Online:2023-02-28 Published:2023-03-07
  • Contact: Yi YANG

摘要:

RNA种类繁多且功能多样,是细胞活动的核心分子之一。RNA代谢调控对于基因和RNA功能研究、细胞生命活动解析以及疾病治疗手段的开发都是至关重要的。为了深入研究RNA时间、空间分布以及功能机制,科学家们一直在追求可以在活细胞内对RNA分子活动进行精密控制的技术,这也是近些年生命科学领域的研究热点之一。目前基于基因编辑、转录调控等可以控制RNA转录生成的技术已较为成熟,但对于RNA转录后代谢的控制技术尚在发展与突破阶段。此前,RNA转录后代谢调控工具是通过调节RNA或基于RNA结合蛋白的RNA效应因子来实现的,但它们的时空分辨率较低,很难对RNA转录后代谢进行定时、定量和定位精密调控。光遗传学凭借其独特的高时空分辨率、非侵入性等优势已经被逐步用于发展活细胞RNA代谢时空精确控制技术。目前,基于核苷酸光化学修饰、遗传编码光响应因子的光遗传学工具已经可实现在转录或转录后水平对RNA多种代谢活动的时空精密控制,包括生成、运输、翻译、降解等。本文将介绍RNA代谢调控系统的研究进展,并聚焦于RNA转录后代谢的光遗传学调控技术,同时对其未来发展前景进行了展望。

关键词: 光遗传学, RNA代谢, RNA功能, 时空精密控制, 光控RNA结合蛋白

Abstract:

RNA exhibits complex dynamics and functions at specific times and locations inside cells, which include changes in their expression, degradation, translocation, splicing and other chemical modifications. The precise regulation of RNA metabolism is crucial for the studies of gene and RNA functions, the analysis of cellular activities, as well as the development of treatments for diseases. In order to deeply understand the temporal and spatial distribution and functional mechanism of RNA, scientists are always pursuing technologies that can precisely control the activity of RNA molecules in live cells. There are several gene editing- or transcriptional regulation-based methodologies that can regulate RNA synthesis in live cells. However, technologies for controlling the post-transcriptional metabolic behaviors of RNA are highly desirable, but they are less attained. Traditional methodologies for regulating RNA metabolism, e.g., regulatory RNA or RNA-binding proteins-based synthetic RNA effectors, suffer from low spatiotemporal resolution, making them difficult to dynamically regulate the post-transcriptional RNA metabolism in real time. Optogenetics has been used for precise spatiotemporal control of RNA metabolism in live cells due to its unique advantages of high spatiotemporal resolution and non-invasiveness. At present, photochemical modifications of nucleotides and genetically encoded photosensitive factors-based optogenetic tools have been applied for spatiotemporal control of various RNA metabolism at transcriptional or post-transcriptional levels, including transcription, translocation, translation and degradation. This article introduces recent progress in regulation of RNA metabolism, in particular the optogenetic control of post-transcriptional RNA metabolism, including technologies based on photochemical modified nucleotides, light-induced protein heterodimerization combined with RNA tethering, light-induced interactions between RNA-binding proteins and their cognate RNA motifs. Finally, we highlight prospects on technologies for precise spatiotemporal control of post-transcriptional RNA metabolism. {L-End}

Key words: optogenetics, RNA metabolism, RNA function, precise spatiotemporal control, light-switchable RNA-binding proteins

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