RNA sectors and allosteric function within the ribosome

Allison S. Walker, William P. Russ, Rama Ranganathan, Alanna Schepartz

Research output: Contribution to journalArticlepeer-review

Abstract

The ribosome translates the genetic code into proteins in all domains of life. Its size and complexity demand long-range interactions that regulate ribosome function. These interactions are largely unknown. Here, we apply a global coevolution method, statistical coupling analysis (SCA), to identify coevolving residue networks (sectors) within the 23S ribosomal RNA (rRNA) of the large ribosomal subunit. As in proteins, SCA reveals a hierarchical organization of evolutionary constraints with near-independent groups of nucleotides forming physically contiguous networks within the three-dimensional structure. Using a quantitative, continuous-culture-with-deep-sequencing assay, we confirm that the top two SCA-predicted sectors contribute to ribosome function. These sectors map to distinct ribosome activities, and their origins trace to phylogenetic divergences across all domains of life. These findings provide a foundation to map ribosome allostery, explore ribosome biogenesis, and engineer ribosomes for new functions. Despite differences in chemical structure, protein and RNA enzymes appear to share a common internal logic of interaction and assembly.

Original languageEnglish (US)
Pages (from-to)19879-19887
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number33
DOIs
StatePublished - Aug 2020

Keywords

  • Genetic code expansion
  • Ribosome evolution
  • Synthetic biology
  • Translation

ASJC Scopus subject areas

  • General

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