Analysis of Riboswitch Structure and Function by an Energy Landscape Framework

Giulio Quarta, Namhee Kim, Joseph A. Izzo, Tamar Schlick

Research output: Contribution to journalArticle

Abstract

The thiamine pyrophosphate (TPP) riboswitch employs modular domains for binding TPP to form a platform for gene expression regulation. Specifically, TPP binding triggers a conformational switch in the RNA from a transcriptionally active "on" state to an inactive "off" state that concomitantly causes the formation of a terminator hairpin and halting of transcription. Here, clustering analysis of energy landscapes at different nucleotide lengths suggests a novel computational tool for analysis of the mechanics of transcription elongation in the presence or absence of the ligand. Namely, we suggest that the riboswitch's kinetics are tightly governed by a length-dependent switch, whereby the energy landscape has two clusters available during transcription elongation and where TPP's binding shifts the preference to one form. Significantly, the biologically active and inactive structures determined experimentally matched well the structures predominant in each computational set. These clustering/structural analyses combined with modular computational design suggest design principles that exploit the above features to analyze as well as create new functions and structures of RNA systems.

Original languageEnglish (US)
Pages (from-to)993-1003
Number of pages11
JournalJournal of Molecular Biology
Volume393
Issue number4
DOIs
StatePublished - Nov 6 2009

Fingerprint

Riboswitch
Thiamine Pyrophosphate
Cluster Analysis
RNA
Gene Expression Regulation
Mechanics
Nucleotides
Ligands

Keywords

  • aptamer
  • cluster analysis
  • energy landscape
  • gene regulation
  • thiamine pyrophosphate (TPP) riboswitch

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Analysis of Riboswitch Structure and Function by an Energy Landscape Framework. / Quarta, Giulio; Kim, Namhee; Izzo, Joseph A.; Schlick, Tamar.

In: Journal of Molecular Biology, Vol. 393, No. 4, 06.11.2009, p. 993-1003.

Research output: Contribution to journalArticle

Quarta, Giulio ; Kim, Namhee ; Izzo, Joseph A. ; Schlick, Tamar. / Analysis of Riboswitch Structure and Function by an Energy Landscape Framework. In: Journal of Molecular Biology. 2009 ; Vol. 393, No. 4. pp. 993-1003.
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