Model-Free RNA Sequence and Structure Alignment Informed by SHAPE Probing Reveals a Conserved Alternate Secondary Structure for 16S rRNA

Christopher A. Lavender, Ronny Lorenz, Ge Zhang, Rita Tamayo, Ivo L. Hofacker, Kevin M. Weeks

Research output: Research - peer-reviewArticle

  • 10 Citations

Abstract

Discovery and characterization of functional RNA structures remains challenging due to deficiencies in de novo secondary structure modeling. Here we describe a dynamic programming approach for model-free sequence comparison that incorporates high-throughput chemical probing data. Based on SHAPE probing data alone, ribosomal RNAs (rRNAs) from three diverse organisms – the eubacteria E. coli and C. difficile and the archeon H. volcanii – could be aligned with accuracies comparable to alignments based on actual sequence identity. When both base sequence identity and chemical probing reactivities were considered together, accuracies improved further. Derived sequence alignments and chemical probing data from protein-free RNAs were then used as pseudo-free energy constraints to model consensus secondary structures for the 16S and 23S rRNAs. There are critical differences between these experimentally-informed models and currently accepted models, including in the functionally important neck and decoding regions of the 16S rRNA. We infer that the 16S rRNA has evolved to undergo large-scale changes in base pairing as part of ribosome function. As high-quality RNA probing data become widely available, structurally-informed sequence alignment will become broadly useful for de novo motif and function discovery.

LanguageEnglish (US)
Article numbere1004126
JournalPLoS Computational Biology
Volume11
Issue number5
DOIs
StatePublished - May 1 2015

Fingerprint

Secondary Structure
Alternate
Alignment
Model
secondary structure
RNA
alignment
16S Ribosomal RNA
Sequence Alignment
ribosomal RNA
Ribosomal RNA
chemical
23S Ribosomal RNA
Archaea
Ribosomes
Base Pairing
Neck
Escherichia coli
Bacteria
Proteins

ASJC Scopus subject areas

  • Computational Theory and Mathematics
  • Modeling and Simulation
  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Molecular Biology
  • Ecology
  • Cellular and Molecular Neuroscience

Cite this

Model-Free RNA Sequence and Structure Alignment Informed by SHAPE Probing Reveals a Conserved Alternate Secondary Structure for 16S rRNA. / Lavender, Christopher A.; Lorenz, Ronny; Zhang, Ge; Tamayo, Rita; Hofacker, Ivo L.; Weeks, Kevin M.

In: PLoS Computational Biology, Vol. 11, No. 5, e1004126, 01.05.2015.

Research output: Research - peer-reviewArticle

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