Structure, folding and flexibility of co-transcriptional RNA origami
By Ewan K. S. McRae, H. Rasmussen, Jianfang Liu, Andreas Bøggild, Michael T. A. Nguyen, Néstor Sampedro Vallina, T. Boesen, J. Pedersen, G. Ren, Cody W. Geary and 1 more. 2023
62 citations recorded by the source corpus.
RNA origami is a method for designing RNA nanostructures that can self-assemble through co-transcriptional folding with applications in nanomedicine and synthetic biology. However, to advance the method further, an improved understanding of RNA structural properties and folding principles is required. Here we use cryogenic electron microscopy to study RNA origami sheets and bundles at sub-nanometre resolution revealing structural parameters of kissing-loop and crossover motifs, which are used to improve designs. In RNA bundle designs, we discover a kinetic folding trap that forms during folding and is only released after 10 h. Exploration of the conformational landscape of several RNA designs reveal the flexibility of helices and structural motifs. Finally, sheets and bundles are combined to construct a multidomain satellite shape, which is characterized by individual-particle cryo-electron tomography to reveal the domain flexibility. Together, the study provides a structural basis for future improvements to the design cycle of genetically encoded RNA nanodevices. RNA nanostructures can be designed to fold during transcription, but the solution structure has remained elusive. Here the authors use cryogenic electron microscopy to determine the structure of a panel of RNA origami shapes and uncover the design and folding principles.
Subfields: Immunology, Molecular Biology
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In Molecular Biology
- Andriy Kryshtafovych
- John Moult
- Janusz M. Bujnicki
- Rhiju Das
- Maya Topf
- Yang Zhang
- Torsten Schwede
- Daniel J. Rigden
Citations in the corpus
- CASP15 cryoEM protein and RNA targets: refinement and analysis using experimental maps (2023, background): “R1138 a 6-helix bundle at 4.9 Å resolution A particularly interesting example for cryoEM refinement of RNA models was the predictions and refinement for R1138, a designed 6-helix bundle of RNA with a clasp (6HBC) 36 .”
- RNA target highlights in CASP15: Evaluation of predicted models by structure providers (2023, background): “44,45 We anticipate that incorporation of structural dynamics and co-transcriptional folding pathways will be the next major hurdle for RNA structure prediction.”