Reversible Control
of RNA Splicing by Photoswitchable
Small Molecules
Posted on 2023-06-05 - 20:43
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
light-dependent 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.
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Zhang, Lei; Xie, Xiulan; Djokovic, Nemanja; Nikolic, Katarina; Kosenkov, Dmitri; Abendroth, Frank; et al. (1753). Reversible Control
of RNA Splicing by Photoswitchable
Small Molecules. ACS Publications. Collection. https://doi.org/10.1021/jacs.3c03275
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AUTHORS (7)
LZ
Lei Zhang
XX
Xiulan Xie
ND
Nemanja Djokovic
KN
Katarina Nikolic
DK
Dmitri Kosenkov
FA
Frank Abendroth
OV
Olalla Vázquez
KEYWORDS
fluorescence polarization measurementsdependent exon inclusioncurrent optochemical toolkittarget functional proteinprecisely provide rnaprotein levelswork pioneerstime controltheoretical calculationssynthetic photoswitchesspatiotemporal resolutionrna researchrna functionreversible controlphotopharmacology modulationphotochemical characterizationnmr experimentsliving cellfirst demonstratedderived cellsconfirmed lightbased processesbased assaysavailable means