Reversible Control of RNA Splicing by Photoswitchable Small Molecules
Authorized Users Only
2023
Authors
Zhang, LeiXie, Xiulan
Đoković, Nemanja

Nikolić, Katarina

Kosenkov, Dmitri

Abendroth, Frank
Vázquez, Olalla
Article (Published version)

Metadata
Show full item recordAbstract
Dynamics are intrinsic to both RNA function and
structure. Yet, the available means to precisely provide RNA-based
processes with spatiotemporal resolution are scarce. Here, our
work pioneers a reversible approach to regulate RNA splicing
within primary patient-derived cells by synthetic photoswitches.
Our small molecule enables conditional real-time control at mRNA
and protein levels. NMR experiments, together with theoretical
calculations, photochemical characterization, fluorescence polarization
measurements, and living cell-based assays, confirmed lightdependent
exon inclusion as well as an increase in the target
functional protein. Therefore, we first demonstrated the potential
of photopharmacology modulation in splicing, tweaking the
current optochemical toolkit. The timeliness on the consolidation
of RNA research as the driving force toward therapeutical innovation holds the promise that our approach will contribute to
redrawing the vision of RNA.
Source:
Journal of the American Chemical Society, 2023, 145, 23, 12783-12792Publisher:
- American Chemical Society
Funding / projects:
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200161 (University of Belgrade, Faculty of Pharmacy) (RS-200161)
- Modeling and Numerical Simulations of Complex Many-Body Systems (RS-171017)
- The German Research Council (DFG; AB 792/1-1 for F.A. and SPP1926 “Next Generation Optogenetics”: 61502867 DFG; VA1002/4-1 for O.V.).
DOI: 10.1021/jacs.3c03275
ISSN: 0002-7863
PubMed: 37276581
WoS: 001010449500001
Scopus: 2-s2.0-85163405665
Collections
Institution/Community
PharmacyTY - JOUR AU - Zhang, Lei AU - Xie, Xiulan AU - Đoković, Nemanja AU - Nikolić, Katarina AU - Kosenkov, Dmitri AU - Abendroth, Frank AU - Vázquez, Olalla PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4913 AB - Dynamics are intrinsic to both RNA function and structure. Yet, the available means to precisely provide RNA-based processes with spatiotemporal resolution are scarce. Here, our work pioneers a reversible approach to regulate RNA splicing within primary patient-derived cells by synthetic photoswitches. Our small molecule enables conditional real-time control at mRNA and protein levels. NMR experiments, together with theoretical calculations, photochemical characterization, fluorescence polarization measurements, and living cell-based assays, confirmed lightdependent exon inclusion as well as an increase in the target functional protein. Therefore, we first demonstrated the potential of photopharmacology modulation in splicing, tweaking the current optochemical toolkit. The timeliness on the consolidation of RNA research as the driving force toward therapeutical innovation holds the promise that our approach will contribute to redrawing the vision of RNA. PB - American Chemical Society T2 - Journal of the American Chemical Society T1 - Reversible Control of RNA Splicing by Photoswitchable Small Molecules VL - 145 IS - 23 SP - 12783 EP - 12792 DO - 10.1021/jacs.3c03275 ER -
@article{ author = "Zhang, Lei and Xie, Xiulan and Đoković, Nemanja and Nikolić, Katarina and Kosenkov, Dmitri and Abendroth, Frank and Vázquez, Olalla", year = "2023", abstract = "Dynamics are intrinsic to both RNA function and structure. Yet, the available means to precisely provide RNA-based processes with spatiotemporal resolution are scarce. Here, our work pioneers a reversible approach to regulate RNA splicing within primary patient-derived cells by synthetic photoswitches. Our small molecule enables conditional real-time control at mRNA and protein levels. NMR experiments, together with theoretical calculations, photochemical characterization, fluorescence polarization measurements, and living cell-based assays, confirmed lightdependent exon inclusion as well as an increase in the target functional protein. Therefore, we first demonstrated the potential of photopharmacology modulation in splicing, tweaking the current optochemical toolkit. The timeliness on the consolidation of RNA research as the driving force toward therapeutical innovation holds the promise that our approach will contribute to redrawing the vision of RNA.", publisher = "American Chemical Society", journal = "Journal of the American Chemical Society", title = "Reversible Control of RNA Splicing by Photoswitchable Small Molecules", volume = "145", number = "23", pages = "12783-12792", doi = "10.1021/jacs.3c03275" }
Zhang, L., Xie, X., Đoković, N., Nikolić, K., Kosenkov, D., Abendroth, F.,& Vázquez, O.. (2023). Reversible Control of RNA Splicing by Photoswitchable Small Molecules. in Journal of the American Chemical Society American Chemical Society., 145(23), 12783-12792. https://doi.org/10.1021/jacs.3c03275
Zhang L, Xie X, Đoković N, Nikolić K, Kosenkov D, Abendroth F, Vázquez O. Reversible Control of RNA Splicing by Photoswitchable Small Molecules. in Journal of the American Chemical Society. 2023;145(23):12783-12792. doi:10.1021/jacs.3c03275 .
Zhang, Lei, Xie, Xiulan, Đoković, Nemanja, Nikolić, Katarina, Kosenkov, Dmitri, Abendroth, Frank, Vázquez, Olalla, "Reversible Control of RNA Splicing by Photoswitchable Small Molecules" in Journal of the American Chemical Society, 145, no. 23 (2023):12783-12792, https://doi.org/10.1021/jacs.3c03275 . .