RNA转录后代谢时空精密控制技术  

Technologies for precise spatiotemporal control of post-transcriptional RNA metabolism

作　　者：刘韧玫 李乐诗 杨小燕[1,2] 陈显军 杨弋[1,2] LIU Renmei;LI Leshi;YANG Xiaoyan;CHEN Xianjun;YANG Yi(Optogenetics&Synthetic Biology Interdisciplinary Research Center,State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China;Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China;School of Bioengineering,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[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

出　　处：《合成生物学》2023年第1期141-164,共24页Synthetic Biology Journal

基　　金：国家重点研发计划(2022YFC3400100,2019YFA0904800,2021ZD0202200);国家自然科学基金(32121005,21937004,32150028,91857202,32001026)。

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。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 posttranscriptional 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, lightinduced interactions between RNA-binding proteins and their cognate RNA motifs. Finally, we highlight prosp

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 

分 类 号：Q816[生物学—生物工程]