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Comment
. 2022 Jul 21;7(1):246.
doi: 10.1038/s41392-022-01069-w.

The beginning of a new era: pioneering direct screens for RNA modulators

F X Reymond Sutandy  1 , Rebecca George Tharyan  1 , Christian Münch  2   3   4
Affiliations
Comment

The beginning of a new era: pioneering direct screens for RNA modulators

F X Reymond Sutandy et al. Signal Transduct Target Ther. .
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
An ALIS-based RNA-binding screen revealed compound X1 as a small molecule that specifically targets Xist RNA and modulates its activity. a ALIS screening was performed targeting the RepA domain of Xist RNA. Compound X22 was identified in the screen and further validated. Hit expansion studies with X22 were carried out and resulting affinities evaluated and ranked. Ultimately, Kd analyses were used to validate several hits, including the original hit X22, and its analog compound X1. Compound X1 yielded the highest affinity to RepA and was used to perform functional assays to modulate Xist RNA both in vitro and in cells. b The Xist RNA recruits PRC1, PRC2 and SPEN to inactivate the X chromosome by epigenetic modification (left). X1 disrupts the Xist RNA structure upon binding and compromises Xist RNA-protein interactions, resulting in pertained X chromosome activation (right).
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References

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