Issue 110, 2014

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

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

Supplementary files

Article information

Article type
Communication
Submitted
22 Sep 2014
Accepted
18 Nov 2014
First published
20 Nov 2014
This article is Open Access
Creative Commons BY license

RSC Adv., 2014,4, 64901-64904

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

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