Abstract
RNA transcripts containing the hammerhead ribozyme have been engineered to self-destruct in the presence of specific nucleoside 3',5'-cyclic monophosphate compounds. These RNA molecular switches were created by a new combinatorial strategy termed 'allosteric selection,' which favors the emergence of ribozymes that rapidly self-cleave only when incubated with their corresponding effector compounds. Representative RNAs exhibit 5,000- fold activation upon cGMP or cAMP addition, display precise molecular recognition characteristics, and operate with catalytic rates that match those exhibited by unaltered ribozymes. These findings demonstrate that a vast number of ligand-responsive ribozymes with dynamic structural characteristics can be generated in a massively parallel fashion. Moreover, optimized allosteric ribozymes could serve as highly selective sensors of chemical agents or as unique genetic control elements for the programmed destruction of cellular RNAs.
| Original language | English |
|---|---|
| Pages (from-to) | 1062-1071 |
| Number of pages | 10 |
| Journal | Nature Structural Biology |
| Volume | 6 |
| Issue number | 11 |
| DOIs | |
| State | Published - 1999 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Genetics
- Structural Biology
Cite this
Allosteric selection of ribozymes that respond to the second messengers cGMP and cAMP. / Koizumi, Makoto; Soukup, Garrett; Kerr, J. N Q; Breaker, Ronald R.
In: Nature Structural Biology, Vol. 6, No. 11, 1999, p. 1062-1071.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Allosteric selection of ribozymes that respond to the second messengers cGMP and cAMP
AU - Koizumi, Makoto
AU - Soukup, Garrett
AU - Kerr, J. N Q
AU - Breaker, Ronald R.
PY - 1999
Y1 - 1999
N2 - RNA transcripts containing the hammerhead ribozyme have been engineered to self-destruct in the presence of specific nucleoside 3',5'-cyclic monophosphate compounds. These RNA molecular switches were created by a new combinatorial strategy termed 'allosteric selection,' which favors the emergence of ribozymes that rapidly self-cleave only when incubated with their corresponding effector compounds. Representative RNAs exhibit 5,000- fold activation upon cGMP or cAMP addition, display precise molecular recognition characteristics, and operate with catalytic rates that match those exhibited by unaltered ribozymes. These findings demonstrate that a vast number of ligand-responsive ribozymes with dynamic structural characteristics can be generated in a massively parallel fashion. Moreover, optimized allosteric ribozymes could serve as highly selective sensors of chemical agents or as unique genetic control elements for the programmed destruction of cellular RNAs.
AB - RNA transcripts containing the hammerhead ribozyme have been engineered to self-destruct in the presence of specific nucleoside 3',5'-cyclic monophosphate compounds. These RNA molecular switches were created by a new combinatorial strategy termed 'allosteric selection,' which favors the emergence of ribozymes that rapidly self-cleave only when incubated with their corresponding effector compounds. Representative RNAs exhibit 5,000- fold activation upon cGMP or cAMP addition, display precise molecular recognition characteristics, and operate with catalytic rates that match those exhibited by unaltered ribozymes. These findings demonstrate that a vast number of ligand-responsive ribozymes with dynamic structural characteristics can be generated in a massively parallel fashion. Moreover, optimized allosteric ribozymes could serve as highly selective sensors of chemical agents or as unique genetic control elements for the programmed destruction of cellular RNAs.
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U2 - 10.1038/14947
DO - 10.1038/14947
M3 - Article
VL - 6
SP - 1062
EP - 1071
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 11
ER -