Harnessing Molecular Recognition for Small-Molecule-Mediated Reversible Photochemical Control Over mRNA Translation

被引：0

作者：

Parmar, Shaifaly ^{[1
]}

Tenney, Logan ^{[1
]}

Liang, Xiao ^{[1
]}

Routzahn, John T. ^{[1
]}

Sibley, Christopher D. ^{[1
]}

Schneekloth Jr, John S. ^{[1
]}

机构：

[1] NCI, Ctr Canc Res, Chem Biol Lab, Frederick, MD 21702 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2025年 / 64卷 / 22期

关键词：

Aptamers; Chemical biology; Photochemistry; RNA; Translation; CROSS-LINKING REACTION; 3-CYANOVINYLCARBAZOLE NUCLEOSIDE; APTAMER;

D O I：

10.1002/anie.202503078

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Chemical probes that control the function of complex RNA molecules offer unique opportunities to interrogate biological systems. In this study, we demonstrate that a small molecule ligand selectively recognizes and undergoes traceless, reversible photocrosslinking to PreQ1 RNA aptamers. This effect is selective and dependent on both the chemical structure and RNA sequence/structure. A homogeneously modified, caged mRNA construct containing a PreQ1 aptamer and an eGFP or wild type p53 coding sequence displayed repressed translation in vitro or in cells until irradiated with 302 nm light, resulting in cleavage of the photocage and restoration of translation. This method demonstrates for the first time that aptamer-based molecular recognition of a small molecule ligand can be used to precisely and photochemically activate the translation of a complex mRNA in cells.

引用

页数：9

共 31 条

[1] Synthetic ligands for PreQ1 riboswitches provide structural and mechanistic insights into targeting RNA tertiary structure [J].

Connelly, Colleen M. ;

Numata, Tomoyuki ;

Boer, Robert E. ;

Moon, Michelle H. ;

Sinniah, Ranu S. ;

Barchi, Joseph J. ;

Ferre-D'Amare, Adrian R. ;

Schneekloth, John S., Jr. .

NATURE COMMUNICATIONS, 2019, 10 (1)

[2] Spatiotemporal control of microRNA function using light-activated antagomirs [J].

Connelly, Colleen M. ;

Uprety, Rajendra ;

Hemphill, James ;

Deiters, Alexander .

MOLECULAR BIOSYSTEMS, 2012, 8 (11) :2987-2993

[3] Strong Inhibitory Effects of Antisense Probes on Gene Expression through Ultrafast RNA Photocrosslinking [J].

Fujimoto, Kenzo ;

Yang-Chun, Hung ;

Nakamura, Shigetaka .

CHEMISTRY-AN ASIAN JOURNAL, 2019, 14 (11) :1912-1916

[4] Details of the Ultrafast DNA Photo-Cross-Linking Reaction of 3-Cyanovinylcarbazole Nucleoside: Cis-Trans Isomeric Effect and the Application for SNP-Based Genotyping [J].

Fujimoto, Kenzo ;

Yamada, Asuka ;

Yoshimura, Yoshinaga ;

Tsukaguch, Tadashi ;

Sakamoto, Takashi .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (43) :16161-16167

[5] Geometric Effect on the Photocrosslinking Reaction between 3-Cyanovinylcarbazole Nucleoside and Pyrimidine Base in DNA/RNA Heteroduplex [J].

Fujimoto, Kenzo ;

Kishi, Satomi ;

Sakamoto, Takashi .

PHOTOCHEMISTRY AND PHOTOBIOLOGY, 2013, 89 (05) :1095-1099

[6] Site-Specific Cytosine to Uracil Transition by Using Reversible DNA Photo-crosslinking [J].

Fujimoto, Kenzo ;

Konishi-Hiratsuka, Kaoru ;

Sakamoto, Takashi ;

Yoshimura, Yoshinaga .

CHEMBIOCHEM, 2010, 11 (12) :1661-1664

[7] Optochemical control of RNA interference in mammalian cells [J].

Govan, Jeane M. ;

Young, Douglas D. ;

Lusic, Hrvoje ;

Liu, Qingyang ;

Lively, Mark O. ;

Deiters, Alexander .

NUCLEIC ACIDS RESEARCH, 2013, 41 (22) :10518-10528

[8] Caged oligonucleotides for bidirectional photomodulation of let-7 miRNA in zebrafish embryos [J].

Griepenburg, Julianne C. ;

Ruble, Brittani K. ;

Dmochowski, Ivan J. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (20) :6198-6204

[9] Discriminating Self and Non-Self by RNA: Roles for RNA Structure, Misfolding, and Modification in Regulating the Innate Immune Sensor PKR [J].

Hull, Chelsea M. ;

Bevilacqua, Philip C. .

ACCOUNTS OF CHEMICAL RESEARCH, 2016, 49 (06) :1242-1249

[10] Comparison of a PreQ1 Riboswitch Aptamer in Metabolite-bound and Free States with Implications for Gene Regulation [J].

Jenkins, Jermaine L. ;

Krucinska, Jolanta ;

McCarty, Reid M. ;

Bandarian, Vahe ;

Wedekind, Joseph E. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (28) :24626-24637

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