Branched kissing loops for the construction of diverse RNA homooligomeric nanostructures

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  • Di Liu, Department of Chemistry, University of Chicago, Chicago, IL, USA.
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  • Cody W Geary, Department of Molecular Biology and Genetics, Aarhus University, Aarhus C., Denmark Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C., Denmark., Departments of Bioengineering, Computational and Mathematical Sciences, and Computation and Neural Systems, California Institute of Technology, Pasadena, CA, USA.
  • ,
  • Gang Chen, Department of Chemistry, University of Chicago, Chicago, IL, USA., Department of Chemistry, University of Central Florida, Orlando, FL, USA.
  • ,
  • Yaming Shao, Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.
  • ,
  • Mo Li, Department of Chemistry, Purdue University, West Lafayette, IN, USA.
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  • Chengde Mao, Department of Chemistry, Purdue University, West Lafayette, IN, USA.
  • ,
  • Ebbe S Andersen
  • Joseph A Piccirilli, Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.
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  • Paul W K Rothemund, Departments of Bioengineering, Computational and Mathematical Sciences, and Computation and Neural Systems, California Institute of Technology, Pasadena, CA, USA. pwkr@dna.caltech.edu.
  • ,
  • Yossi Weizmann, Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel. yweizmann@bgu.ac.il.

In biological systems, large and complex structures are often assembled from multiple simpler identical subunits. This strategy-homooligomerization-allows efficient genetic encoding of structures and avoids the need to control the stoichiometry of multiple distinct units. It also allows the minimal number of distinct subunits when designing artificial nucleic acid structures. Here, we present a robust self-assembly system in which homooligomerizable tiles are formed from intramolecularly folded RNA single strands. Tiles are linked through an artificially designed branched kissing-loop motif, involving Watson-Crick base pairing between the single-stranded regions of a bulged helix and a hairpin loop. By adjusting the tile geometry to gain control over the curvature, torsion and the number of helices, we have constructed 16 different linear and circular structures, including a finite-sized three-dimensional cage. We further demonstrate cotranscriptional self-assembly of tiles based on branched kissing loops, and show that tiles inserted into a transfer RNA scaffold can be overexpressed in bacterial cells.

Original languageEnglish
JournalNature Chemistry
ISSN1755-4330
DOIs
Publication statusPublished - 20 Jan 2020
Externally publishedYes

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