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Fuzzy RNA recognition by the Trypanosoma brucei editosome

The assembly of high molecular mass ribonucleoprotein complexes typically relies on the binary interaction of defined RNA sequences or precisely folded RNA motifs with dedicated RNA-binding domains on the protein side. Here we describe a new molecular recognition principle of RNA molecules by a high...

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Autores principales: Leeder, Wolf-Matthias, Geyer, Felix Klaus, Göringer, Hans Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178004/
https://www.ncbi.nlm.nih.gov/pubmed/35580050
http://dx.doi.org/10.1093/nar/gkac357
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author Leeder, Wolf-Matthias
Geyer, Felix Klaus
Göringer, Hans Ulrich
author_facet Leeder, Wolf-Matthias
Geyer, Felix Klaus
Göringer, Hans Ulrich
author_sort Leeder, Wolf-Matthias
collection PubMed
description The assembly of high molecular mass ribonucleoprotein complexes typically relies on the binary interaction of defined RNA sequences or precisely folded RNA motifs with dedicated RNA-binding domains on the protein side. Here we describe a new molecular recognition principle of RNA molecules by a high molecular mass protein complex. By chemically probing the solvent accessibility of mitochondrial pre-mRNAs when bound to the Trypanosoma brucei editosome, we identified multiple similar but non-identical RNA motifs as editosome contact sites. However, by treating the different motifs as mathematical graph objects we demonstrate that they fit a consensus 2D-graph consisting of 4 vertices (V) and 3 edges (E) with a Laplacian eigenvalue of 0.5477 (λ(2)). We establish that synthetic 4V(3E)-RNAs are sufficient to compete for the editosomal pre-mRNA binding site and that they inhibit RNA editing in vitro. Furthermore, we demonstrate that only two topological indices are necessary to predict the binding of any RNA motif to the editosome with a high level of confidence. Our analysis corroborates that the editosome has adapted to the structural multiplicity of the mitochondrial mRNA folding space by recognizing a fuzzy continuum of RNA folds that fit a consensus graph descriptor.
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spelling pubmed-91780042022-06-09 Fuzzy RNA recognition by the Trypanosoma brucei editosome Leeder, Wolf-Matthias Geyer, Felix Klaus Göringer, Hans Ulrich Nucleic Acids Res RNA and RNA-protein complexes The assembly of high molecular mass ribonucleoprotein complexes typically relies on the binary interaction of defined RNA sequences or precisely folded RNA motifs with dedicated RNA-binding domains on the protein side. Here we describe a new molecular recognition principle of RNA molecules by a high molecular mass protein complex. By chemically probing the solvent accessibility of mitochondrial pre-mRNAs when bound to the Trypanosoma brucei editosome, we identified multiple similar but non-identical RNA motifs as editosome contact sites. However, by treating the different motifs as mathematical graph objects we demonstrate that they fit a consensus 2D-graph consisting of 4 vertices (V) and 3 edges (E) with a Laplacian eigenvalue of 0.5477 (λ(2)). We establish that synthetic 4V(3E)-RNAs are sufficient to compete for the editosomal pre-mRNA binding site and that they inhibit RNA editing in vitro. Furthermore, we demonstrate that only two topological indices are necessary to predict the binding of any RNA motif to the editosome with a high level of confidence. Our analysis corroborates that the editosome has adapted to the structural multiplicity of the mitochondrial mRNA folding space by recognizing a fuzzy continuum of RNA folds that fit a consensus graph descriptor. Oxford University Press 2022-05-17 /pmc/articles/PMC9178004/ /pubmed/35580050 http://dx.doi.org/10.1093/nar/gkac357 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle RNA and RNA-protein complexes
Leeder, Wolf-Matthias
Geyer, Felix Klaus
Göringer, Hans Ulrich
Fuzzy RNA recognition by the Trypanosoma brucei editosome
title Fuzzy RNA recognition by the Trypanosoma brucei editosome
title_full Fuzzy RNA recognition by the Trypanosoma brucei editosome
title_fullStr Fuzzy RNA recognition by the Trypanosoma brucei editosome
title_full_unstemmed Fuzzy RNA recognition by the Trypanosoma brucei editosome
title_short Fuzzy RNA recognition by the Trypanosoma brucei editosome
title_sort fuzzy rna recognition by the trypanosoma brucei editosome
topic RNA and RNA-protein complexes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178004/
https://www.ncbi.nlm.nih.gov/pubmed/35580050
http://dx.doi.org/10.1093/nar/gkac357
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