Computational design of three-dimensional RNA structure and function

Joseph D. Yesselman; Daniel Eiler; Erik D. Carlson; Michael R. Gotrik; Anne E. d’Aquino; Alexandra N. Ooms; Wipapat Kladwang; Paul D. Carlson; Xuesong Shi; David A. Costantino; Daniel Herschlag; Julius B. Lucks; Michael C. Jewett; Jeffrey S. Kieft; Rhiju Das

doi:10.1038/s41565-019-0517-8

Computational design of three-dimensional RNA structure and function

Joseph D. Yesselman, Daniel Eiler, Erik D. Carlson, Michael R. Gotrik, Anne E. d’Aquino, Alexandra N. Ooms, Wipapat Kladwang, Paul D. Carlson, Xuesong Shi, David A. Costantino, Daniel Herschlag, Julius B. Lucks, Michael C. Jewett, Jeffrey S. Kieft, Rhiju Das^*

^*Corresponding author for this work

Chemical and Biological Engineering

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

Abstract

RNA nanotechnology seeks to create nanoscale machines by repurposing natural RNA modules. The field is slowed by the current need for human intuition during three-dimensional structural design. Here, we demonstrate that three distinct problems in RNA nanotechnology can be reduced to a pathfinding problem and automatically solved through an algorithm called RNAMake. First, RNAMake discovers highly stable single-chain solutions to the classic problem of aligning a tetraloop and its sequence-distal receptor, with experimental validation from chemical mapping, gel electrophoresis, solution X-ray scattering and crystallography with 2.55 Å resolution. Second, RNAMake automatically generates structured tethers that integrate 16S and 23S ribosomal RNAs into single-chain ribosomal RNAs that remain uncleaved by ribonucleases and assemble onto messenger RNA. Third, RNAMake enables the automated stabilization of small-molecule binding RNAs, with designed tertiary contacts that improve the binding affinity of the ATP aptamer and improve the fluorescence and stability of the Spinach RNA in cell extracts and in living Escherichia coli cells.

Original language	English (US)
Pages (from-to)	866-873
Number of pages	8
Journal	Nature nanotechnology
Volume	14
Issue number	9
DOIs	https://doi.org/10.1038/s41565-019-0517-8
State	Published - Sep 1 2019

Funding

We thank S. Bonilla for assistance in performing the native gel assays and A. Watkins for discussions about ribosome tether design. We thank the Straight lab for graciously providing X. laevis whole cell lysate. This work was supported by the National Institutes of Health, through NIGMS MIRA R35 GM122579 (R.D.), R01 GM121487 (R.D.), New Innovator Award 1DP2GM110838 (J.B.L.), Ruth L. Kirschstein National Research Service Award Postdoctoral Fellowships GM112294 (J.D.Y.) and GM100953 (D.E.), P01 GM066275 (D.H.) and R35 GM118070 (J.S.K.), a Stanford School of Medicine Discovery Innovation Award (R.D.), Army Research Office W911NF-16-1-0372 (M.C.J.), the National Science Foundation through MCB-1716766 (M.C.J.), Career Award 1452441 (J.B.L.) and Graduate Research Fellowship DGE-1324585 (A.E.D.), the David and Lucile Packard Foundation (M.C.J.) and the Camille Dreyfus Teacher-Scholar Program (M.C.J.).

ASJC Scopus subject areas

Bioengineering
Atomic and Molecular Physics, and Optics
Biomedical Engineering
General Materials Science
Condensed Matter Physics
Electrical and Electronic Engineering

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10.1038/s41565-019-0517-8

Cite this

Yesselman, J. D., Eiler, D., Carlson, E. D., Gotrik, M. R., d’Aquino, A. E., Ooms, A. N., Kladwang, W., Carlson, P. D., Shi, X., Costantino, D. A., Herschlag, D., Lucks, J. B., Jewett, M. C., Kieft, J. S., & Das, R. (2019). Computational design of three-dimensional RNA structure and function. Nature nanotechnology, 14(9), 866-873. https://doi.org/10.1038/s41565-019-0517-8

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Computational design of three-dimensional RNA structure and function

Abstract

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ASJC Scopus subject areas

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Computationally designed mini tetraloop-tetraloop receptor by the RNAMake program - construct 6 (miniTTR 6)

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Computational design of three-dimensional RNA structure and function

Abstract

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ASJC Scopus subject areas

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Computationally designed mini tetraloop-tetraloop receptor by the RNAMake program - construct 6 (miniTTR 6)

Cite this