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

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  • Erin R. Calkins, University of California at Santa Barbara
  • ,
  • Paul Zakrevsky, University of California at Santa Barbara
  • ,
  • Vasken L. Keleshian, University of California at Santa Barbara
  • ,
  • Eduardo G. Aguilar, University of California at Santa Barbara
  • ,
  • Cody Geary
  • Luc Jaeger, University of California at Santa Barbara

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.

Original languageEnglish
JournalNucleic Acids Research
Pages (from-to)480-494
Number of pages15
Publication statusPublished - Jan 2019
Externally publishedYes

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