PT  - JOURNAL ARTICLE
AU  - Wolf-Matthias Leeder
AU  - H. Ulrich Göringer
TI  - Fuzzy RNA-recognition by the <em>Trypanosoma brucei</em> editosome
AID  - 10.1101/2021.06.10.446919
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.10.446919
4099  - http://biorxiv.org/content/early/2021/06/10/2021.06.10.446919.short
4100  - http://biorxiv.org/content/early/2021/06/10/2021.06.10.446919.full
AB  - The recognition of RNA-molecules by proteins and protein complexes is a critical step on all levels of gene expression. Typically, the generated ribonucleoprotein complexes rely 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 nonidentical 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 0.523 (λ2). We establish that a synthetic 4V(3E)-RNA is sufficient to compete for the editosomal pre-mRNA binding site and that it is able to inhibit RNA-editing in vitro. 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. This provides a mechanism on how the protein complex is able to bind the structurally pleomorphic pool of pre- and partially edited mRNAs. We speculate that other fuzzy RNA-recognition motifs exist especially for proteins that interact with multiple RNA-species.Competing Interest StatementThe authors have declared no competing interest.