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Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch

Author

Listed:
  • Alexander Serganov

    (Structural Biology Program, Memorial Sloan-Kettering Cancer Center)

  • Anna Polonskaia

    (Structural Biology Program, Memorial Sloan-Kettering Cancer Center)

  • Anh Tuân Phan

    (Structural Biology Program, Memorial Sloan-Kettering Cancer Center)

  • Ronald R. Breaker

    (Cellular and Developmental Biology and Howard Hughes Medical Institute, Yale University)

  • Dinshaw J. Patel

    (Structural Biology Program, Memorial Sloan-Kettering Cancer Center)

Abstract

Riboswitches as drug targets Genes are commonly turned on or off by protein factors that respond to cellular signals. The recent discovery of riboswitches, regulatory elements within some messenger RNAs, proved that RNA can also detect essential metabolites and control genes. Two structural studies throw new light on the riboswitch system. Serganov et al. use X-ray diffraction to establish the three-dimensional structure of a riboswitch from Escherichia coli bound to its target, a vitamin B1 derivative. These findings reveal how RNA folds to form a precise pocket for its target and how the antibiotic pyrithiamine acts by tricking the riboswitch. This suggests a new drug design strategy for antibacterials and antifungals targeting riboswitches. Montange and Batey have solved the structure of a bacterial riboswitch RNA bound to S-adenosyl methionine. Its complex folded structure reveals how ligand binding leads structural changes that prevent further transcription.

Suggested Citation

  • Alexander Serganov & Anna Polonskaia & Anh Tuân Phan & Ronald R. Breaker & Dinshaw J. Patel, 2006. "Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch," Nature, Nature, vol. 441(7097), pages 1167-1171, June.
  • Handle: RePEc:nat:nature:v:441:y:2006:i:7097:d:10.1038_nature04740
    DOI: 10.1038/nature04740
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    Cited by:

    1. Daniel B. Haack & Boris Rudolfs & Shouhong Jin & Alexandra Khitun & Kevin M. Weeks & Navtej Toor, 2025. "Scaffold-enabled high-resolution cryo-EM structure determination of RNA," Nature Communications, Nature, vol. 16(1), pages 1-17, December.

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