26. Lee J, Lee KH, Jeon J, Dragulescu-Andrasi A,
Xiao F, Rao J (2010) Combining SELEX
screening and rational design to develop
light-up fluorophore-RNA aptamer pairs for
RNA tagging. ACS Chem Biol 5
(11):1065–1074. https://doi.org/10.1021/
cb1001894
27. Sunbul M, Jaschke A (2013) Contactmediated quenching for RNA imaging in bacteria with a fluorophore-binding aptamer.
Angew
Chem
Int
Ed
Engl
52
(50):13401–13404.
https://doi.org/10.
1002/anie.201306622
28. Arora A, Sunbul M, Jaschke A (2015) Dualcolour imaging of RNAs using quencher- and
fluorophore-binding aptamers. Nucleic Acids
Res 43(21):e144. https://doi.org/10.1093/
nar/gkv718
29. Sunbul M, Jaschke A (2018) SRB-2: a promiscuous rainbow aptamer for live-cell RNA
imaging. Nucleic Acids Res 46(18):e110.
https://doi.org/10.1093/nar/gky543
30. Wirth R, Gao P, Nienhaus GU, Sunbul M,
Jaschke A (2019) SiRA: a silicon rhodaminebinding aptamer for live-cell super-resolution
RNA imaging. J Am Chem Soc 141
(18):7562–7571. https://doi.org/10.1021/
jacs.9b02697
31. Murata A, Sato S, Kawazoe Y, Uesugi M
(2011) Small-molecule fluorescent probes
for specific RNA targets. Chem Commun
(Camb) 47(16):4712–4714. https://doi.
org/10.1039/c1cc10393h
32. Braselmann E, Wierzba AJ, Polaski JT,
Chrominski M, Holmes ZE, Hung ST,
Batan D, Wheeler JR, Parker R, Jimenez R,
Gryko D, Batey RT, Palmer AE (2018) A
multicolor riboswitch-based platform for
imaging of RNA in live mammalian cells.
Nat Chem Biol 14(10):964–971. https://
doi.org/10.1038/s41589-018-0103-7
33. Ellington AD, Szostak JW (1990) In vitro
selection of RNA molecules that bind specific
ligands.
Nature
346(6287):818–822.
https://doi.org/10.1038/346818a0
34. Tuerk C, Gold L (1990) Systematic evolution
of ligands by exponential enrichment: RNA
ligands to bacteriophage T4 DNA polymerase. Science 249(4968):505–510. https://
doi.org/10.1126/science.2200121
35. Filonov GS, Moon JD, Svensen N, Jaffrey SR
(2014) Broccoli: rapid selection of an RNA
mimic of green fluorescent protein by
fluorescence-based selection and directed
evolution. J Am Chem Soc 136
(46):16299–16308.
https://doi.org/10.
1021/ja508478x
36. Heim R, Cubitt AB, Tsien RY (1995)
Improved green fluorescence. Nature 373
(6516):663–664. https://doi.org/10.1038/
373663b0
37. Gotrik M, Sekhon G, Saurabh S,
Nakamoto M, Eisenstein M, Soh HT (2018)
Direct selection of fluorescence-enhancing
RNA aptamers. J Am Chem Soc 140
(10):3583–3591. https://doi.org/10.1021/
jacs.7b10724
38. Kraus GA, Jeon I, Nilsen-Hamilton M, Awad
AM, Banerjee J, Parvin B (2008) Fluorinated
analogs of malachite green: synthesis and toxicity. Molecules 13(4):986–994. https://doi.
org/10.3390/molecules13040986
39. Endoh T, Ohyama T, Sugimoto N (2019)
RNA-capturing
microsphere
particles
(R-CAMPs) for optimization of functional
aptamers. Small 15(26):e1805062. https://
doi.org/10.1002/smll.201805062
40. Ryckelynck M, Baudrey S, Rick C, Marin A,
Coldren F, Westhof E, Griffiths AD (2015)
Using droplet-based microfluidics to improve
the catalytic properties of RNA under
multiple-turnover conditions. RNA 21
(3):458–469. https://doi.org/10.1261/rna.
048033.114
41. Autour A, Ryckelynck M (2017) Ultrahighthroughput improvement and discovery of
enzymes using droplet-based microfluidic
screening. Micromachines 8(4):128. https://
doi.org/10.3390/mi8040128
42. Autour A, Westhof E, Ryckelynck M (2016)
iSpinach: a fluorogenic RNA aptamer optimized for in vitro applications. Nucleic Acids
Res 44(6):2491–2500. https://doi.org/10.
1093/nar/gkw083
43. Autour A, S CYJ ADC, Abdolahzadeh A,
Galli A, Panchapakesan SSS, Rueda D,
Ryckelynck M, Unrau PJ (2018) Fluorogenic
RNA Mango aptamers for imaging small
non-coding RNAs in mammalian cells. Nat
Commun 9(1):656. https://doi.org/10.
1038/s41467-018-02993-8
44. Ketterer S, Fuchs D, Weber W, Meier M
(2015) Systematic reconstruction of binding
and stability landscapes of the fluorogenic
aptamer spinach. Nucleic Acids Res. https://
doi.org/10.1093/nar/gkv944
45. Ketterer S, Gladis L, Kozica A, Meier M
(2016) Engineering and characterization of
fluorogenic glycine riboswitches. Nucleic
Acids Res 44(12):5983–5992. https://doi.
org/10.1093/nar/gkw465
46. Henderson CA, Rail CA, Butt LE, Vincent
HA, Callaghan AJ (2019) Generation of
small molecule-binding RNA arrays and their
Light-Up RNA Aptamers
97
Xiao F, Rao J (2010) Combining SELEX
screening and rational design to develop
light-up fluorophore-RNA aptamer pairs for
RNA tagging. ACS Chem Biol 5
(11):1065–1074. https://doi.org/10.1021/
cb1001894
27. Sunbul M, Jaschke A (2013) Contactmediated quenching for RNA imaging in bacteria with a fluorophore-binding aptamer.
Angew
Chem
Int
Ed
Engl
52
(50):13401–13404.
https://doi.org/10.
1002/anie.201306622
28. Arora A, Sunbul M, Jaschke A (2015) Dualcolour imaging of RNAs using quencher- and
fluorophore-binding aptamers. Nucleic Acids
Res 43(21):e144. https://doi.org/10.1093/
nar/gkv718
29. Sunbul M, Jaschke A (2018) SRB-2: a promiscuous rainbow aptamer for live-cell RNA
imaging. Nucleic Acids Res 46(18):e110.
https://doi.org/10.1093/nar/gky543
30. Wirth R, Gao P, Nienhaus GU, Sunbul M,
Jaschke A (2019) SiRA: a silicon rhodaminebinding aptamer for live-cell super-resolution
RNA imaging. J Am Chem Soc 141
(18):7562–7571. https://doi.org/10.1021/
jacs.9b02697
31. Murata A, Sato S, Kawazoe Y, Uesugi M
(2011) Small-molecule fluorescent probes
for specific RNA targets. Chem Commun
(Camb) 47(16):4712–4714. https://doi.
org/10.1039/c1cc10393h
32. Braselmann E, Wierzba AJ, Polaski JT,
Chrominski M, Holmes ZE, Hung ST,
Batan D, Wheeler JR, Parker R, Jimenez R,
Gryko D, Batey RT, Palmer AE (2018) A
multicolor riboswitch-based platform for
imaging of RNA in live mammalian cells.
Nat Chem Biol 14(10):964–971. https://
doi.org/10.1038/s41589-018-0103-7
33. Ellington AD, Szostak JW (1990) In vitro
selection of RNA molecules that bind specific
ligands.
Nature
346(6287):818–822.
https://doi.org/10.1038/346818a0
34. Tuerk C, Gold L (1990) Systematic evolution
of ligands by exponential enrichment: RNA
ligands to bacteriophage T4 DNA polymerase. Science 249(4968):505–510. https://
doi.org/10.1126/science.2200121
35. Filonov GS, Moon JD, Svensen N, Jaffrey SR
(2014) Broccoli: rapid selection of an RNA
mimic of green fluorescent protein by
fluorescence-based selection and directed
evolution. J Am Chem Soc 136
(46):16299–16308.
https://doi.org/10.
1021/ja508478x
36. Heim R, Cubitt AB, Tsien RY (1995)
Improved green fluorescence. Nature 373
(6516):663–664. https://doi.org/10.1038/
373663b0
37. Gotrik M, Sekhon G, Saurabh S,
Nakamoto M, Eisenstein M, Soh HT (2018)
Direct selection of fluorescence-enhancing
RNA aptamers. J Am Chem Soc 140
(10):3583–3591. https://doi.org/10.1021/
jacs.7b10724
38. Kraus GA, Jeon I, Nilsen-Hamilton M, Awad
AM, Banerjee J, Parvin B (2008) Fluorinated
analogs of malachite green: synthesis and toxicity. Molecules 13(4):986–994. https://doi.
org/10.3390/molecules13040986
39. Endoh T, Ohyama T, Sugimoto N (2019)
RNA-capturing
microsphere
particles
(R-CAMPs) for optimization of functional
aptamers. Small 15(26):e1805062. https://
doi.org/10.1002/smll.201805062
40. Ryckelynck M, Baudrey S, Rick C, Marin A,
Coldren F, Westhof E, Griffiths AD (2015)
Using droplet-based microfluidics to improve
the catalytic properties of RNA under
multiple-turnover conditions. RNA 21
(3):458–469. https://doi.org/10.1261/rna.
048033.114
41. Autour A, Ryckelynck M (2017) Ultrahighthroughput improvement and discovery of
enzymes using droplet-based microfluidic
screening. Micromachines 8(4):128. https://
doi.org/10.3390/mi8040128
42. Autour A, Westhof E, Ryckelynck M (2016)
iSpinach: a fluorogenic RNA aptamer optimized for in vitro applications. Nucleic Acids
Res 44(6):2491–2500. https://doi.org/10.
1093/nar/gkw083
43. Autour A, S CYJ ADC, Abdolahzadeh A,
Galli A, Panchapakesan SSS, Rueda D,
Ryckelynck M, Unrau PJ (2018) Fluorogenic
RNA Mango aptamers for imaging small
non-coding RNAs in mammalian cells. Nat
Commun 9(1):656. https://doi.org/10.
1038/s41467-018-02993-8
44. Ketterer S, Fuchs D, Weber W, Meier M
(2015) Systematic reconstruction of binding
and stability landscapes of the fluorogenic
aptamer spinach. Nucleic Acids Res. https://
doi.org/10.1093/nar/gkv944
45. Ketterer S, Gladis L, Kozica A, Meier M
(2016) Engineering and characterization of
fluorogenic glycine riboswitches. Nucleic
Acids Res 44(12):5983–5992. https://doi.
org/10.1093/nar/gkw465
46. Henderson CA, Rail CA, Butt LE, Vincent
HA, Callaghan AJ (2019) Generation of
small molecule-binding RNA arrays and their
Light-Up RNA Aptamers
97