基于核糖开关的新型基因表达调控系统的应用

doi:10.13560/j.cnki.biotech.bull.1985.2017.02.006

摘要/Abstract

摘要： 核糖开关是能对细胞环境的改变做出反应的顺式作用元件,通过改变自身的构象实现对基因表达的调控。基于核糖开关调控方式简洁,无需蛋白质参与,响应迅速,且自身片段小,结构简单,易于设计和改造等特性使其在生物医学领域体现出诸多应用优势。对核糖开关的结构,调节机理以及这种新型基因表达调控系统在基因治疗、抗生素新靶点的开发、病毒疫苗的安全控制、新型核糖选择器和生物体内传感器的应用进行了综述,旨为启示我国核糖开关的新型应用。

关键词: 核糖开关, 基因表达调控系统, 机理

Abstract: Riboswitches are cis-acting elements that can respond to the environmental changes of the cell by altering its conformation to achieve the regulation of gene expression. Due to its characteristics of simple regulation system without proteins involved,response fast,short sequences with simple structure,and easy to design and modify,applying it in biomedical area should be in superiority. The review addresses the advance of the structure and regulation mechanism of riboswitches,as well as the applications of this novel regulation system of gene expression in gene therapy,the development of novel target for antibiotic,the safety switch for virus vaccine,and the new riboselectors and biosensors,aiming at inspiring the application of riboswitches in China.

Key words: riboswitch, regulation system of gene expression, mechanism

熊莹喆, 曹苑青, 肖玲慧, 李招发. 基于核糖开关的新型基因表达调控系统的应用[J]. 生物技术通报, 2017, 33(2): 41-46.

XIONG Ying-zhe, CAO Yuan-qin, XIAO Ling-hui, LI Zhao-fa. Applications of Riboswitch-based Novel Regulation System of Gene Expression[J]. Biotechnology Bulletin, 2017, 33(2): 41-46.

参考文献

[1] Winkler W, Nahvi A, Breaker RR. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression[J]. Nature, 2002, 419（6910）：952-956.
[2] Nahvi A, Sudarsan N, Ebert M, et al. Genetic control by a metabolite binging Mrna[J]. Chem Biol, 2002, 9（9）：1043-1049.
[3] Breaker RR. Complex riboswitches[J]. Science, 2008, 319（5871）：1795-1797.
[4] 王佳稳, 冯婧娴, 林俊生, 等. 适体核酶型人工核糖开关的设计[J]. 中国生物工程杂志, 2014, 34（2）：59-64.
[5] Grundy FJ, Henkin TM. From ribosome to riboswitch：control of gene expression in bacteria by RNA structural rearrangements[J]. Critical Reviews in Biochemistry & Molecular Biology, 2006, 41（6）：329-338.
[6] Barrick JE, Breaker RR. The distributions, mechanisms, and structures of metabolite-binding riboswitches[J]. Genome Biology, 2007, 8（11）：R239.
[7] Serganov A, Nudler E. A decade of riboswitches[J]. Cell, 2013, 152（152）：17-24.
[8] Serganov A, Yuan YR, Pikovskaya O, et al. Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs[J]. Chemistry & Biology, 2004, 11（12）：1729-1741.
[9] Serganov A, Polonskaia A, Phan AT, et al. Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch[J]. Nature, 2006, 441（7097）：1167-1171.
[10] Gilbert SD, Rambo RP, Van TD, et al. Structure of the SAM-II riboswitch bound to S-adenosylmethionine[J]. Nature Structural & Molecular Biology, 2008, 15（2）：177-182.
[11] Li S, Breaker RR. Fluoride enhances the activity of fungicides that destabilize cell membranes[J]. Bioorganic & Medicinal Chemistry Letters, 2012, 22（9）：3317-3322.
[12] Liberman JA, Salim M, Krucinska J, et al. Structure of a class II preQ1 riboswitch reveals ligand recognition by a new fold[J]. Nature Chemical Biology, 2013, 9（6）：353-355.
[13] 贾东方, 林俊生, 刁勇. 抗生素开发的新靶点：核糖开关[J]. 药学学报, 2013, 48（9）：1361-1368.
[14] Furukawa K, Gu H, Sudarsan N, et al. Identification of ligand analogues that control c-di-GMP riboswitches[J]. Acs Chemical Biology, 2012, 7（8）：1436-1443.
[15] Furukawa K, Ramesh A, Zhou Z, et al. Bacterial riboswitches cooperatively bind Ni 2+ , or Co 2+ , ions and control expression of heavy metal transporters[J]. Molecular Cell, 2015, 57（6）：1088-1098.
[16] Price IR, Gaballa A, Ding F, et al. Mn 2+ -sensing mechanisms of yybP-ykoY orphan riboswitches[J]. Mol Cell, 2015, 57（6）：1110-1123.
[17] Meyer MM, Hammond MC, Salinas Y, et al. Challenges of ligand identification for riboswitch candidates[J]. RNA Biol, 2011, 8 （1）：5-10.
[18] Watson PY, Fedor MJ. The ydaO motif is an ATP-sensing riboswitch in Bacillus subtilis[J]. Nat Chem Biol, 2012, 8（12）：963- 965.
[19] 冯婧娴. 人工核酶核糖开关调控转基因表达的性能及优化[D]. 厦门：华侨大学, 2015.
[20] Mandal M, Boese B, Barrick JE, et al. Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria[J]. Cell, 2003, 113（5）：577-586.
[21] Gilbert SD, Montange RK, Stoddard CD, et al. Structural studies of the purine and SAM binding riboswitches[J]. Cold Spring Harbor Symposia on Quantitative Biology, 2006, 71：259-268.
[22] Hollands K, Proshkin S, Sklyarova S, et al. Riboswitch control of Rho-dependent transcription termination[J]. PNAS, 2012, 109（14）：5376-5381.
[23] Haller A, Rieder U, Aigner M, et al. Conformational capture of the SAM-II riboswitch[J]. Nature Chemical Biology, 2011, 7（6）：393-400.
[24] Reining A, Nozinovic S, Schlepckow K, et al. Three-state mecha-nism couples ligand and temperature sensing in riboswitches[J]. Nature, 2013, 499（7458）：355-359.
[25] Collins JA, Irnov I, Baker S, et al. Mechanism of mRNA destabilization by the glmS ribozyme[J]. Genes & Development, 2007, 21（24）：3356-3368.
[26] Alberts B. The breakthroughs of 2009[J]. Science, 2009, 326（5960）：1589.
[27] Klauser B, Atanasov J, Siewert LK, et al. Ribozyme-based aminoglycoside switches of gene expression engineered by genetic selection in S. cerevisiae[J]. Acs Synthetic Biology, 2014, 4（5）：516-525.
[28] 杨会勇, 刁勇, 林俊生, 等. 新型基因表达调控元件——人工核糖开关的构建及筛选[J]. 生物工程学报, 2012, 28（2）：134-143.
[29] 冯婧娴, 王佳稳, 林俊生, 刁勇. 核酶核糖开关在基因治疗中的应用及挑战[J]. 药学学报, 2014, 49（11）：1504-1511.
[30] Chen YY, Jensen MC, Smolke CD. Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems[J]. PNAS, 2010, 107（19）：8531-8536.
[31] Liang JC, Bloom RJ, Smolke CD. Engineering biological systems with synthetic RNA molecules[J]. Mol Cell, 2011, 43（6）：915-926.
[32] Theuretzbacher U. Accelerating resistance, inadequate antibacterial drug pipelines and international responses[J]. International Journal of Antimicrobial Agents, 2012, 39（4）：295-299.
[33] Blount KF, Breaker RR. Riboswitches as antibacterial drug targets[J]. Nature Biotechnology, 2006, 24（12）：1558-1564.
[34] Jia X, Zhang J, Sun W, et al. Riboswitch control of aminoglycoside antibiotic resistance[J]. Cell, 2013, 152（1-2）：68-81.
[35] Russell SJ, Peng KW, Bell JC. Oncolytic virotherapy[J]. Nat Biotechnol, 2012, 30（7）：658-670.
[36] Ketzer P, Kaufmann JK, Engelhardt S, et al. Artificial riboswitches for gene expression and replication control of DNA and RNAviruses[J]. PNAS, 2014, 111（5）：E554-E562.
[37] Dietrich JA, McKee AE, Keasling JD. High-throughput metabolic engineering：advances in small-molecule screening and selection[J]. Annu Rev Biochem, 2010, 79（1）：563-590.
[38] Jang S, Yang J, Sang WS, et al. Chapter seventeen-riboselector：riboswitch-based synthetic selection device to expedite evolution of metabolite-producing microorganisms[J]. Methods in Enzymology, 2015, 550：341-362.
[39] Yang J, Seo SW, Jang S, et al. Synthetic RNA devices to expedite the evolution of metabolite-producing microbes[J]. Nat Commun, 2013, 4（1413）：1- 7.
[40] Muranaka N, Sharma V, Nomura Y, et al. An efficient platform for genetic selection and screening of gene switches in Escherichia coli[J]. Nucleic Acids Research, 2009, 37（5）：e39.
[41] Park M, Tsai SL, Chen W. Microbial biosensors：engineered microorganisms as the sensing machinery[J]. Sensors, 2013, 13（5）：5777-5795.
[42] Avciadali M, Wilhelm N, Perle N, et al. Absolute quantification of cell-bound DNA aptamers during SELEX[J]. Nucleic Acid Ther, 2013, 23（2）：125-130.
[43] Win MN, Smolke CD. A modular and extensible RNA-based gene-regulatory platform for engineering cellular function[J]. PNAS, 2007, 104（36）：14283-14288.
[44] Hull CM, Anmangandla A, Bevilacqua PC. Bacterial riboswitches and ribozymes potently activate the human innate immune sensor PKR[J]. ACS Chem Biol, 2016, 11（4）：1118-1127.