TY  - JOUR
A1  - Leeder, W.-Matthias
A1  - Reuß, Andreas J.
A1  - Brecht, Michael
A1  - Kratz, Katja
A1  - Wachtveitl, Josef
A1  - Göringer, H. Ulrich
T1  - Charge reduction and thermodynamic stabilization of substrate RNAs inhibit RNA editing
T2  - PLoS One
N2  - African trypanosomes cause a parasitic disease known as sleeping sickness. Mitochondrial transcript maturation in these organisms requires a RNA editing reaction that is characterized by the insertion and deletion of U-nucleotides into otherwise non-functional mRNAs. Editing represents an ideal target for a parasite-specific therapeutic intervention since the reaction cycle is absent in the infected host. In addition, editing relies on a macromolecular protein complex, the editosome, that only exists in the parasite. Therefore, all attempts to search for editing interfering compounds have been focused on molecules that bind to proteins of the editing machinery. However, in analogy to other RNA-driven biochemical pathways it should be possible to stall the reaction by targeting its substrate RNAs. Here we demonstrate inhibition of editing by specific aminoglycosides. The molecules bind into the major groove of the gRNA/pre-mRNA editing substrates thereby causing a stabilization of the RNA molecules through charge compensation and an increase in stacking. The data shed light on mechanistic details of the editing process and identify critical parameters for the development of new trypanocidal compounds.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37168
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-371687
SN  - 1932-6203
N1  - Copyright: © 2015 Leeder et al. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
VL  - 10
IS  - (3): e0118940
PB  - PLoS
CY  - Lawrence, Kan.
ER  -