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Fuzzy RNA recognition by the Trypanosoma brucei editosome

Leeder, Wolf-Matthias ; Geyer, Felix Klaus ; Göringer, H. Ulrich (2022)
Fuzzy RNA recognition by the Trypanosoma brucei editosome.
In: Nucleic acids research, 50 (10)
doi: 10.1093/nar/gkac357
Artikel, Bibliographie

Kurzbeschreibung (Abstract)

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 (λ2). 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.

Typ des Eintrags: Artikel
Erschienen: 2022
Autor(en): Leeder, Wolf-Matthias ; Geyer, Felix Klaus ; Göringer, H. Ulrich
Art des Eintrags: Bibliographie
Titel: Fuzzy RNA recognition by the Trypanosoma brucei editosome
Sprache: Englisch
Publikationsjahr: 17 Mai 2022
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Nucleic acids research
Jahrgang/Volume einer Zeitschrift: 50
(Heft-)Nummer: 10
DOI: 10.1093/nar/gkac357
Kurzbeschreibung (Abstract):

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 (λ2). 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.

ID-Nummer: pmid:35580050
Zusätzliche Informationen:

Artikel-ID: gkac357

Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Genregulation und RNA-Therapeutika
Hinterlegungsdatum: 23 Mai 2022 12:04
Letzte Änderung: 14 Jun 2022 06:42
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