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Deducing putative ancestral forms of GNRA/receptor interactions from the ribosome

Calkins, Erin R. and Zakrevsky, Paul and Keleshian, Vasken L. and Aguilar, Eduardo G. and Geary, Cody and Jaeger, Luc (2019) Deducing putative ancestral forms of GNRA/receptor interactions from the ribosome. Nucleic Acids Research, 47 (1). pp. 480-494. ISSN 0305-1048. PMCID PMC6326782. https://resolver.caltech.edu/CaltechAUTHORS:20190412-104543880

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Abstract

Stable RNAs rely on a vast repertoire of long-range interactions to assist in the folding of complex cellular machineries such as the ribosome. The universally conserved L39/H89 interaction is a long-range GNRA-like/receptor interaction localized in proximity to the peptidyl transferase center of the large subunit of the ribosome. Because of its central location, L39/H89 likely originated at an early evolutionary stage of the ribosome and played a significant role in its early function. However, L39/H89 self-assembly is impaired outside the ribosomal context. Herein, we demonstrate that structural modularity principles can be used to re-engineer L39/H89 to self-assemble in vitro. The new versions of L39/H89 improve affinity and loop selectivity by several orders of magnitude and retain the structural and functional features of their natural counterparts. These versions of L39/H89 are proposed to be ancestral forms of L39/H89 that were capable of assembling and folding independently from proteins and post-transcriptional modifications. This work demonstrates that novel RNA modules can be rationally designed by taking advantage of the modular syntax of RNA. It offers the prospect of creating new biochemical models of the ancestral ribosome and increases the tool kit for RNA nanotechnology and synthetic biology.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1093/nar/gky1111DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6326782/PubMed CentralArticle
ORCID:
AuthorORCID
Geary, Cody0000-0003-2083-4259
Jaeger, Luc0000-0001-9068-348X
Additional Information:© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. Received July 27, 2018; Revised October 17, 2018; Editorial Decision October 20, 2018; Accepted October 22, 2018. Published: 12 November 2018. The authors thank Maria del Carmen Jaeger and Dr Pascal Auffinger for fruitful discussions. This work is dedicated to the memory of Prof. Albert Jaeger and Prof. Jérome Lejeune. Funding: National Aeronautics and Space Administration (NASA) [80NSSC17K0031 to L.J., in part]; UCSB Academic Senate, Intramural Research Grants (to L.J.). Funding for open access charge: NASA [80NSSC17K0031]. Conflict of interest statement. None declared.
Funders:
Funding AgencyGrant Number
NASA80NSSC17K0031
University of California, Santa BarbaraUNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC6326782
Record Number:CaltechAUTHORS:20190412-104543880
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190412-104543880
Official Citation:Erin R Calkins, Paul Zakrevsky, Vasken L Keleshian, Eduardo G Aguilar, Cody Geary, Luc Jaeger, Deducing putative ancestral forms of GNRA/receptor interactions from the ribosome, Nucleic Acids Research, Volume 47, Issue 1, 10 January 2019, Pages 480–494, https://doi.org/10.1093/nar/gky1111
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94692
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:12 Apr 2019 22:19
Last Modified:21 May 2020 21:47

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