Genotype-phenotype map of an RNA-ligand complex
Puchta, O.; Sobczyk, G.; Smer-Barreto, V.; Ireland, H.; Vendrell, M.; Oyarzun, D. A.; Bujnicki, J. M. A.; Whyte, G.; Kudla, G.
Show abstract
RNA-ligand interactions play important roles in biology and biotechnology, but they often involve complex three-dimensional folding of RNA and are difficult to predict. To systematically explore the phenotypic landscape of an RNA-ligand complex, we used microarrays to investigate all possible single and double mutants of the 49-nt RNA aptamer Broccoli bound to the fluorophore DFHBI-1T. We collected more than seven million fluorescence measurements in varying conditions, and inferred dissociation rate constants, spectral shifts, and intragenic epistasis. Our results reveal an unexpectedly complex phenotypic landscape, in which mutations near the fluorophore binding pocket modulated magnesium-, potassium- and fluorophore-binding and fluorescence spectra, while distal mutations influenced structural stability and fluorescence intensity. We trained a machine learning model that accurately predicted RNA secondary structure from local epistatic interactions, despite the presence of G-quadruplexes and other noncanonical structures. Our experimental platform will facilitate the discovery and analysis of new RNA-ligand interactions.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Overcoming the design, build, test (DBT) bottleneck for synthesis of nonrepetitive protein-RNA binding cassettes for RNA applications 96%
- Insights into the secondary structural ensembles of the full SARS-CoV-2 RNA genome in infected cells 96%
- High-throughput interrogation of programmed ribosomal frameshifting in human cells 95%
Similar papers in this journal
Similar papers in this journal
- Mechanism of transcription modulation by the transcription-repair coupling factor 95%
- rec-Y2H matrix screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins 95%
- Yeast Ssd1 is a non-enzymatic member of the RNase II family with an alternative RNA recognition interface 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.