活细胞<strong>RNA</strong>成像技术及其在生物医学中应用研究进展

doi:10.3724/zdxbyxb-2022-0017

浙江大学学报（医学版）

2022, Vol. 51

Issue (3): 362-372 DOI: 10.3724/zdxbyxb-2022-0017

综述

活细胞RNA成像技术及其在生物医学中应用研究进展

孙萍萍^1,²,邹炜^1,^2,*(

)

1. 浙江大学医学院附属第四医院，浙江义乌 322000
2. 浙江大学医学院转化医学研究院，浙江杭州 310058

Research progress of live-cell RNA imaging techniques

SUN Pingping^1,²,ZOU Wei^1,^2,*(

)

1. The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, Zhejiang Province, China;
2. Institute of Translational Medicine, Zhejiang University, Hangzhou 310058, China

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摘要：

RNA可与各种核酸及蛋白质相互作用，在多种生理和病理过程中发挥重要的调控作用，其生物学过程高度动态。追踪活细胞中的RNA动态对理解基因表达的时空调控以及RNA的调控功能至关重要。基于荧光蛋白的RNA标记系统包括MS2/MCP系统、PP7/PCP系统、boxB/λN22和CRISPR-Cas系统等，其中MS2/MCP系统目前应用最为广泛，其具有结合稳定、信噪比高等优点，局限性是RNA成像的实现需要对靶RNA进行基因编辑，这可能导致靶RNA特性的潜在改变。近期开发的CRISPR-dCas13系统不需要对RNA进行改造，但其局限性在于CRISPR RNA效率的不确定性，且信噪比较低。基于荧光染料的RNA标记系统包括分子信标和荧光基团-适体对，其中分子信标具有高特异性和较高信噪比，而荧光基团–适体对Pepper系统和Mango系统在RNA成像的信噪比上更具有优势，但也需要对靶RNA进行基因编辑。活细胞RNA成像技术可应用于观察并研究RNA转录、剪接、转运、翻译（特指信使RNA）和亚细胞定位，有助于研究细胞分化等生物学过程以及细胞适应外界环境时的转录调控机制，有利于理解RNA行为异常导致的各种疾病的致病机制以及寻找潜在的治疗靶点。本文综述了活细胞RNA成像技术的发展和运用，并比较了各种方法的优势和不足。

关键词： 活细胞RNA成像; 基因表达; 转录调控; 信使RNA; 非编码RNA；综述

Abstract:

RNA molecules play diverse roles in many physiological and pathological processes as they interact with various nucleic acids and proteins. The various biological processes of RNA are highly dynamic. Tracking RNA dynamics in living cells is crucial for a better understanding of the spatiotemporal control of gene expression and the regulatory roles of RNA. Genetically encoded RNA-tagging systems include MS2/MCP, PP7/PCP, boxB/λN22 and CRISPR-Cas. The MS2/MCP system is the most widely applied, and it has the advantages of stable binding and high signal-to-noise ratio, while the realization of RNA imaging requires gene editing of the target RNA, which may change the characteristics of the target RNA. Recently developed CRISPR-dCas13 system does not require RNA modification, but the uncertainty in CRISPR RNA (crRNA) efficiency and low signal-to-noise ratio are its limitations. Fluorescent dye-based RNA-tagging systems include molecular beacons and fluorophore-binding aptamers. The molecular beacons have high specificity and high signal-to-noise ratio; Mango and Peppers outperform the other RNA-tagging system in signal-to-noise, but they also need gene editing. Live-cell RNA imaging allows us to visualize critical steps of RNA activities, including transcription, splicing, transport, translation (for message RNA only) and subcellular localization. It will contribute to studying biological processes such as cell differentiation and the transcriptional regulation mechanism when cells adapt to the external environment, and it improves our understanding of the pathogenic mechanism of various diseases caused by abnormal RNA behavior and helps to find potential therapeutic targets. This review provides an overview of current progress of live-cell RNA imaging techniques and highlights their major strengths and limitations.

Key words: Live-cell RNA imaging Gene expression Transcriptional regulation Message RNA Non-coding RNA; Review

收稿日期: 2022-01-23 出版日期: 2022-09-21

CLC:

R394

基金资助: 国家自然科学基金（31970919）

通讯作者: 邹炜 E-mail: zouwei@zju.edu.cn

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引用本文:

孙萍萍,邹炜. 活细胞RNA成像技术及其在生物医学中应用研究进展[J]. 浙江大学学报（医学版）, 2022, 51(3): 362-372.

SUN Pingping,ZOU Wei. Research progress of live-cell RNA imaging techniques. J Zhejiang Univ (Med Sci), 2022, 51(3): 362-372.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0017 或 https://www.zjujournals.com/med/CN/Y2022/V51/I3/362

图 1 MS2/MCP系统成像技术原理示意图融合表达荧光蛋白的MCP二聚体与MS2茎环结合实现RNA成像. MCP：MS2衣壳蛋白.

图 2 PP7/PCP系统成像技术原理示意图融合表达荧光蛋白的PCP二聚体与PP7茎环结合实现RNA成像. PCP：PP7衣壳蛋白.

图 3 boxB/λN22系统成像技术原理示意图融合表达荧光蛋白的λN22单体与boxB茎环结合实现RNA成像.

图 4 CRISPR/dCas13系统成像技术原理示意图在crRNA介导下，融合表达荧光蛋白的dCas13蛋白靶向RNA，实现RNA成像. CRISPR: 成簇的、规律间隔的短回文重复序列； crRNA：CRISPR RNA；dCas：失活的Cas.

图 5 分子信标成像技术原理示意图分子信标探针的两端分别是荧光基团和猝灭基团，一旦与靶RNA结合，两端分开，荧光基团发光.

图 6 RNA适体成像原理示意图单独的染料和RNA适体都不发光，而两者结合会迸发出强烈的荧光.

表 1 活细胞RNA成像技术

图 7 神经元活细胞RNA转录、转运、定位以及翻译过程成像示意图利用活细胞成像技术，在神经元的细胞核中实现转录过程的可视化；也能实现树突和轴突中mRNA的转运、正确定位以及翻译过程的可视化. mRNA：信使RNA.

表 2 活细胞RNA成像技术的应用实例

1	RUDKING T, STOLLARB D. High resolution detection of DNA-RNA hybrids in situ by indirect immunofluorescence[J]Nature, 1977, 265( 5593): 472-473. doi: 10.1038/265472a0
2	FEMINOA M, FAYF S, FOGARTYK, et al.Visualization of single RNA transcripts in situ[J]Science, 1998, 280( 5363): 585-590. doi: 10.1126/science.280.5363.585
3	RAJA, VAN DEN BOGAARDP, RIFKINS A, et al.Imaging individual mRNA molecules using multiple singly labeled probes[J]Nat Methods, 2008, 5( 10): 877-879. doi: 10.1038/nmeth.1253
4	CHENJ, MCSWIGGEND, ÜNALE. Single molecule fluorescence in situ hybridization (smFISH) analysis in budding yeast vegetative growth and meiosis[J]J Vis Exp, 2018, 57774. doi: 10.3791/57774
5	BHADURIA, SANDOVAL-ESPINOSAC, OTERO-GARCIAM, et al.An atlas of cortical arealization identifies dynamic molecular signatures[J]Nature, 2021, 598( 7879): 200-204. doi: 10.1038/s41586-021-03910-8
6	ENGC H L, LAWSONM, ZHUQ, et al.Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH[J]Nature, 2019, 568( 7751): 235-239. doi: 10.1038/s41586-019-1049-y
7	RODRIQUESS G, STICKELSR R, GOEVAA, et al.Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution[J]Science, 2019, 363( 6434): 1463-1467. doi: 10.1126/science.aaw1219
8	SATOH, DASS, SINGERR H, et al.Imaging of dna and RNA in living eukaryotic cells to reveal spatiotemporal dynamics of gene expression[J]Annu Rev Biochem, 2020, 89( 1): 159-187. doi: 10.1146/annurev-biochem-011520-104955
9	BRASELMANNE, RATHBUNC, RICHARDSE M, et al.Illuminating RNA biology: tools for imaging RNA in live mammalian cells[J]Cell Chem Biol, 2020, 27( 8): 891-903. doi: 10.1016/j.chembiol.2020.06.010
10	TUTUCCIE, LIVINGSTONN M, SINGERR H, et al.Imaging mRNA in vivo, from birth to death[J]Annu Rev Biophys, 2018, 47( 1): 85-106. doi: 10.1146/annurev-biophys-070317-033037
11	BERTRANDE, CHARTRANDP, SCHAEFERM, et al.Localization of ASH1 mRNA particles in living yeast[J]Mol Cell, 1998, 2( 4): 437-445. doi: 10.1016/s1097-2765(00)80143-4
12	MURAMOTOT, CANNOND, GIERLINSKIM, et al.Live imaging of nascent RNA dynamics reveals distinct types of transcriptional pulse regulation[J]Proc Natl Acad Sci U S A, 2012, 109( 19): 7350-7355. doi: 10.1073/pnas.1117603109
13	LARSOND R, ZENKLUSEND, WUB, et al.Real-time observation of transcription initiation and elongation on an endogenous yeast gene[J]Science, 2011, 332( 6028): 475-478. doi: 10.1126/science.1202142
14	DAIGLEN, ELLENBERGJ. λN-GFP: an RNA reporter system for live-cell imaging[J]Nat Methods, 2007, 4( 8): 633-636. doi: 10.1038/nmeth1065
15	URBANEKM O, GALKA-MARCINIAKP, OLEJNICZAKM, et al.RNA imaging in living cells——methods and applications[J]RNA Biol, 2014, 11( 8): 1083-1095. doi: 10.4161/RNA.35506
16	YANGL Z, WANGY, LIS Q, et al.Dynamic imaging of RNA in living cells by CRISPR-Cas13 systems[J]Mol Cell, 2019, 76( 6): 981-997.e7. doi: 10.1016/j.molcel.2019.10.024
17	TYAGIS, KRAMERF R. Molecular beacons: probes that fluoresce upon hybridization[J]Nat Biotechnol, 1996, 14( 3): 303-308. doi: 10.1038/nbt0396-303
18	CHENX, ZHANGD, SUN, et al.Visualizing RNA dynamics in live cells with bright and stable fluorescent RNAs[J]Nat Biotechnol, 2019, 37( 11): 1287-1293. doi: 10.1038/s41587-019-0249-1
19	DOLGOSHEINAE V, JENGS C Y, PANCHAPAKESANS S S, et al.RNA mango aptamer-fluorophore: a bright, high-affinity complex for RNA labeling and tracking[J]ACS Chem Biol, 2014, 9( 10): 2412-2420. doi: 10.1021/cb500499x
20	WUJ, ZACCARAS, KHUPERKARD, et al.Live imaging of mRNA using RNA-stabilized fluorogenic proteins[J]Nat Methods, 2019, 16( 9): 862-865. doi: 10.1038/s41592-019-0531-7
21	CHUBBJ R, TRCEKT, SHENOYS M, et al.Transcriptional pulsing of a developmental gene[J]Curr Biol, 2006, 16( 10): 1018-1025. doi: 10.1016/j.cub.2006.03.092
22	FORRESTK M, GAVISE R. Live Imaging of endogenous RNA reveals a diffusion and entrapment mechanism for nanos mRNA localization in drosophila[J]Curr Biol, 2003, 13( 14): 1159-1168. doi: 10.1016/s0960-9822(03)00451-2
23	SHAV-TALY, DARZACQX, SHENOYS M, et al.Dynamics of single mrnps in nuclei of living cells[J]Science, 2004, 304( 5678): 1797-1800. doi: 10.1126/science.1099754
24	LIONNETT, CZAPLINSKIK, DARZACQX, et al.A transgenic mouse for in vivo detection of endogenous labeled mRNA[J]Nat Methods, 2011, 8( 2): 165-170. doi: 10.1038/nmeth.1551
25	YOONY J, WUB, BUXBAUMA R, et al.Glutamate-induced RNA localization and translation in neurons[J]Proc Natl Acad Sci U S A, 2016, 113( 44): doi: 10.1073/pnas.1614267113
26	WUB, MISKOLCIV, SATOH, et al.Synonymous modification results in high-fidelity gene expression of repetitive protein and nucleotide sequences[J]Genes Dev, 2015, 29( 8): 876-886. doi: 10.1101/gad.259358.115
27	GARCIAJ F, PARKERR. MS2 coat proteins bound to yeast mRNAs block 5′ to 3′ degradation and trap mRNA decay products: implications for the localization of mRNAs by MS2-MCP system[J]RNA, 2015, 21( 8): 1393-1395. doi: 10.1261/rna.051797.115
28	HEINRICHS, SIDLERC L, AZZALINC M, et al.Stem-loop RNA labeling can affect nuclear and cytoplasmic mRNA processing[J]RNA, 2017, 23( 2): 134-141. doi: 10.1261/rna.057786.116
29	GARCIAJ F, PARKERR. Ubiquitous accumulation of 3′ mRNA decay fragments in Saccharomyces cerevisiae mRNAs with chromosomally integrated MS2 arrays[J]RNA, 2016, 22( 5): 657-659. doi: 10.1261/rna.056325.116
30	HAIMOVICHG, ZABEZHINSKYD, HAASB, et al.Use of the MS2 aptamer and coat protein for RNA localization in yeast: a response to “MS2 coat proteins bound to yeast mRNAs block 5′ to 3′ degradation and trap mRNA decay products: implications for the localization of mRNAs by MS2-MCP system”[J]RNA, 2016, 22( 5): 660-666. doi: 10.1261/rna.055095.115
31	TUTUCCIE, VERAM, BISWASJ, et al.An improved MS2 system for accurate reporting of the mRNA life cycle[J]Nat Methods, 2018, 15( 1): 81-89. doi: 10.1038/nmeth.4502
32	VERA M, TUTUCCI E, SINGER R H. Imaging single mRNA molecules in mammalian cells using an optimized MS2-MCP system[J]. , 2019, 2038: 3-20
33	XUH, WANGJ, LIANGY, et al.TriTag: an integrative tool to correlate chromatin dynamics and gene expression in living cells[J/OL]Nucleic Acids Res, 2020, 48( 22): e127. doi: 10.1093/nar/gkaa906
34	LIMF, PEABODYD S. RNA recognition site of PP7 coat protein[J]Nucleic Acids Res, 2002, 30( 19): 4138-4144. doi: 10.1093/nar/gkf552
35	LIZ, ZHANGP, ZHANGR, et al.A collection of toolkit strains reveals distinct localization and dynamics of membrane-associated transcripts in epithelia[J]Cell Rep, 2021, 35( 5): 109072. doi: 10.1016/j.celrep.2021.109072
36	HOCINES, RAYMONDP, ZENKLUSEND, et al.Single-molecule analysis of gene expression using two-color RNA labeling in live yeast[J]Nat Methods, 2013, 10( 2): 119-121. doi: 10.1038/nmeth.2305
37	WUB, CHAOJ A, SINGERR H. Fluorescence fluctuation spectroscopy enables quantitative imaging of single mRNA in living cells[J]Biophysl J, 2012, 102( 12): 2936-2944. doi: 10.1016/j.bpj.2012.05.017
38	LANGES, KATAYAMAY, SCHMIDM, et al.Simultaneous transport of different localized mRNA species revealed by live-cell imaging[J]Traffic, 2008, 9( 8): 1256-1267. doi: 10.1111/j.1600-0854.2008.00763.x
39	KÖNIGJ, BAUMANNS, KOEPKEJ, et al.The fungal RNA-binding protein Rrm4 mediates long-distance transport of ubi1 and rho3 mRNAs[J]EMBO J, 2009, 28( 13): 1855-1866. doi: 10.1038/emboj.2009.145
40	SCHÖNBERGERJ, HAMMESU Z, DRESSELHAUST. In vivo visualization of RNA in plants cells using the λN22 system and a GATEWAY-compatible vector series for candidate RNAs[J]Plant J, 2012, 71( 1): 173-181. doi: 10.1111/j.1365-313X.2012.04923.x
41	NELLESD A, FANGM Y, O′CONNELLM R, et al.Programmable RNA tracking in live cells with CRISPR/Cas9[J]Cell, 2016, 165( 2): 488-496. doi: 10.1016/j.cell.2016.02.054
42	ABUDAYYEHO O, GOOTENBERGJ S, KONERMANNS, et al.C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector[J]Science, 2016, 353( 6299): f5573. doi: 10.1126/science.aaf5573
43	SMARGONA A, COXD B T, PYZOCHAN K, et al.Cas13b is a type Ⅵ-B CRISPR-associated RNA-guided RNase differentially regulated by accessory proteins csx27 and csx28[J]Mol Cell, 2017, 65( 4): 618-630.e7. doi: 10.1016/j.molcel.2016.12.023
44	KONERMANNS, LOTFYP, BRIDEAUN J, et al.Transcriptome engineering with RNA-targeting type Ⅵ-D CRISPR effectors[J]Cell, 2018, 173( 3): 665-676.e14. doi: 10.1016/j.cell.2018.02.033
45	XUC, ZHOUY, XIAOQ, et al.Programmable RNA editing with compact CRISPR-Cas13 systems from uncultivated microbes[J]Nat Methods, 2021, 18( 5): 499-506. doi: 10.1038/s41592-021-01124-4
46	KANNANS, ALTAE-TRANH, JINX, et al.Compact RNA editors with small Cas13 proteins[J]Nat Biotechnol, 2022, 40( 2): 194-197. doi: 10.1038/s41587-021-01030-2
47	SANTANGELO P J, ALONAS E, JUNG J, et al. Probes for intracellular RNA imaging in live cells[J]. , 2012, 505: 383-399
48	RICARDO M, LUIS V. Molecular beacons: powerful tools for imaging RNA in living cells[J]. , 2011: 741723
49	MAXWELLD J, TAYLORJ R, NIES. Self-assembled nanoparticle probes for recognition and detection of biomolecules[J]J Am Chem Soc, 2002, 124( 32): 9606-9612. doi: 10.1021/ja025814p
50	SONGS, LIANGZ, ZHANGJ, et al.Gold-nanoparticle-based multicolor nanobeacons for sequence-specific DNA analysis[J]Angew Chem Int Ed, 2009, 48( 46): 8670-8674. doi: 10.1002/anie.200901887
51	CONLONP, YANGC J, WUY, et al.Pyrene excimer signaling molecular beacons for probing nucleic acids[J]J Am Chem Soc, 2008, 130( 1): 336-342. doi: 10.1021/ja076411y
52	CHIC W, LAOY H, LIY S, et al.A quantum dot-aptamer beacon using a DNA intercalating dye as the fret reporter: application to label-free thrombin detection[J]Biosens Bioelectron, 2011, 26( 7): 3346-3352. doi: 10.1016/j.bios.2011.01.015
53	GIFFORDL K, JORDAND, PATTANAYAKV, et al.Stemless self-quenching reporter molecules identify target sequences in mRNA[J]Anal Biochem, 2005, 347( 1): 77-88. doi: 10.1016/j.ab.2005.08.030
54	ZHENGJ, YANGR, SHIM, et al.Rationally designed molecular beacons for bioanalytical and biomedical applications[J]Chem Soc Rev, 2015, 44( 10): 3036-3055. doi: 10.1039/c5cs00020c
55	HANS X, JIAX, MAJ, et al.Molecular beacons: a novel optical diagnostic tool[J]Arch Immunol Ther Exp, 2013, 61( 2): 139-148. doi: 10.1007/s00005-012-0209-7
56	CHENM, MAZ, WUX, et al.A molecular beacon-based approach for live-cell imaging of RNA transcripts with minimal target engineering at the single-molecule level[J]Sci Rep, 2017, 7( 1): 1550. doi: 10.1038/s41598-017-01740-1
57	PAIGEJ S, WUK Y, JAFFREYS R. RNA Mimics of green fluorescent protein[J]Science, 2011, 333( 6042): 642-646. doi: 10.1126/science.1207339
58	AUTOURA, JENGC Y S, CAWTEA D, et al.Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells[J]Nat Commun, 2018, 9( 1): 656. doi: 10.1038/s41467-018-02993-8
59	HANGHWAN L, HEAJI S, JUDITH K. Dynamics of Notch-dependent transcriptional bursting in its native context[J]. , 2019, 50 (4): 426-435. e4
60	ALAMOSS, REIMERA, NIYOGIK K, et al.Quantitative imaging of RNA polymerase Ⅱ activity in plants reveals the single-cell basis of tissue-wide transcriptional dynamics[J]Nat Plants, 2021, 7( 8): 1037-1049. doi: 10.1038/s41477-021-00976-0
61	TSUBOIT, VIANAM P, XUF, et al.Mitochondrial volume fraction and translation duration impact mitochondrial mRNA localization and protein synthesis[J/OL]eLife, 2020, e57814. doi: 10.7554/eLife.57814
62	MARTINR M, RINOJ, CARVALHOC, et al.Live-cell visualization of pre-mRNA splicing with single-molecule sensitivity[J]Cell Rep, 2013, 4( 6): 1144-1155. doi: 10.1016/j.celrep.2013.08.013
63	WANY, ANASTASAKISD G, RODRIGUEZJ, et al.Dynamic imaging of nascent RNA reveals general principles of transcription dynamics and stochastic splice site selection[J]Cell, 2021, 184( 11): 2878-2895.e20. doi: 10.1016/j.cell.2021.04.012
64	DUFOURTJ, BELLECM, TRULLOA, et al.Imaging translation dynamics in live embryos reveals spatial heterogeneities[J]Science, 2021, 372( 6544): 840-844. doi: 10.1126/science.abc3483
65	LEEE K, KIMH H, KUWANOY, et al.hnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies[J]Nat Struct Mol Biol, 2010, 17( 6): 732-739. doi: 10.1038/nsmb.1815
66	RODRIGUEZJ, LARSOND R. Transcription in living cells: molecular mechanisms of bursting[J]Annu Rev Biochem, 2020, 89( 1): 189-212. doi: 10.1146/annurev-biochem-011520-105250
67	TUNNACLIFFEE, CHUBBJ R. What is a transcriptional burst?[J]Trends Genet, 2020, 36( 4): 288-297. doi: 10.1016/j.tig.2020.01.003
68	XUH, SKINNERS O, SOKACA M, et al.Stochastic kinetics of nascent RNA[J]Phys Rev Lett, 2016, 117( 12): 128101. doi: 10.1103/PhysRevLett.117.128101
69	SEPULVEDA L A, XU H, ZHANG J, et al. Measurement of gene regulation in individual cells reveals rapid switching between promoter states[J]. , 2016, 351 (6278): 1218-1222
70	SKINNERS O, XUH, NAGARKAR-JAISWALS, et al.Single-cell analysis of transcription kinetics across the cell cycle[J/OL]eLife, 2016, e12175. doi: 10.7554/eLife.12175
71	HOPPEC, BOWLESJ R, MINCHINGTONT G, et al.Modulation of the promoter activation rate dictates the transcriptional response to graded bmp signaling levels in the drosophila embryo[J]Dev Cell, 2020, 54( 6): 727-741.e7. doi: 10.1016/j.devcel.2020.07.007
72	BISWASJ, LIW, SINGERR H, et al.Imaging organization of RNA processing within the nucleus[J]Cold Spring Harb Perspect Biol, 2021, 13( 12): a039453. doi: 10.1101/cshperspect.a039453
73	KATAOKAN, MATSUMOTOE, MASAKIS. Mechanistic insights of aberrant splicing with splicing factor mutations found in myelodysplastic syndromes[J]Int J Mol Sci, 2021, 22( 15): 7789. doi: 10.3390/ijms22157789
74	BOVAIRDS, PATELD, PADILLAJ C A, et al.Biological functions, regulatory mechanisms, and disease relevance of RNA localization pathways[J]FEBS Lett, 2018, 592( 17): 2948-2972. doi: 10.1002/1873-3468.13228
75	MOORES, JÄRVELINA I, DAVISI, et al.Expanding horizons: new roles for non-canonical RNA-binding proteins in cancer[J]Curr Opin Genet Dev, 2018, 112-120. doi: 10.1016/j.gde.2017.11.006
76	CHIARUTTINIC, VICARIOA, LIZ, et al.Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation[J]Proc Natl Acad Sci U S A, 2009, 106( 38): 16481-16486. doi: 10.1073/pnas.0902833106
77	WANGC, HANB, ZHOUR, et al.Real-time imaging of translation on single mRNA transcripts in live cells[J]Cell, 2016, 165( 4): 990-1001. doi: 10.1016/j.cell.2016.04.040
78	WUB, ELISCOVICHC, YOONY J, et al.Translation dynamics of single mRNAs in live cells and neurons[J]Science, 2016, 352( 6292): 1430-1435. doi: 10.1126/science.aaf1084

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