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Issue 110, 2014

Crystal structure, stability and Ago2 affinity of phosphorodithioate-modified RNAs

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Abstract

Small interfering RNAs (siRNAs) with phosphorodithioate modifications (PS2-RNA) possess favourable properties for use as RNAi therapeutics. Beneficial here is the combining of PS2 and 2′-O-methyl modifications (MePS2). SiRNAs with MePS2 moieties in the sense strand show promising efficacies in vitro and in vivo. Crystal structures of PS2- and MePS2- modified RNAs reveal subtle changes in geometry and hydration compared with natural RNA. A model of an MePS2-RNA–PAZ domain complex points to a hydrophobic effect as the source of the higher affinity of MePS2-RNA for Ago2.

Graphical abstract: Crystal structure, stability and Ago2 affinity of phosphorodithioate-modified RNAs

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Article information


Submitted
22 Sep 2014
Accepted
18 Nov 2014
First published
20 Nov 2014

This article is Open Access

RSC Adv., 2014,4, 64901-64904
Article type
Communication
Author version available

Crystal structure, stability and Ago2 affinity of phosphorodithioate-modified RNAs

P. S. Pallan, X. Yang, M. Sierant, N. D. Abeydeera, T. Hassell, C. Martinez, M. Janicka, B. Nawrot and M. Egli, RSC Adv., 2014, 4, 64901 DOI: 10.1039/C4RA10986D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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