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Mechanistic Debris Generated by Twister Ribozymes.

Ronald R Breaker1

  • 1Department of Molecular, Cellular and Developmental Biology, ‡Department of Molecular Biophysics and Biochemistry, §Howard Hughes Medical Institute, Yale University , New Haven, Connecticut 06520, United States.

ACS Chemical Biology
|February 14, 2017
PubMed
Summary

Twister RNAs are natural ribozymes that cut RNA. Despite existing data, their active site architecture and mechanism remain debated, but resolution is achievable.

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Area of Science:

  • Biochemistry and Molecular Biology
  • RNA catalysis
  • Enzymology

Background:

  • Twister RNAs are a novel class of natural ribozymes.
  • These enzymes catalyze rapid cleavage of RNA backbones.
  • Existing data on twister RNAs is abundant but contains disagreements.

Purpose of the Study:

  • To address the ongoing debates regarding the active site architecture and catalytic mechanism of twister RNAs.
  • To synthesize theoretical, biochemical, and structural data to resolve mechanistic uncertainties.
  • To outline a path forward for understanding this class of ribozymes.

Main Methods:

  • Review and synthesis of existing theoretical, biochemical, and structural data.
  • Comparative analysis of different twister RNA members.
  • Identification of key experimental approaches to resolve mechanistic questions.

Main Results:

  • Disagreements persist concerning the precise active site architecture and mechanism of twister RNAs.
  • The historical pattern of mechanistic debate follows the discovery of new self-cleaving ribozymes.
  • Potential pathways exist to reconcile conflicting data and achieve consensus.

Conclusions:

  • The field is experiencing typical post-discovery debates regarding twister RNA mechanisms.
  • Further focused research integrating multiple data types is necessary.
  • Consensus on twister RNA function can be reached through systematic investigation.