Abstract
We engineered small molecule responsive allosteric ribozymes based on the genomic hepatitis delta virus (HDV) ribozyme by replacing the P4-L4 stem-loop with an RNA aptamer through a connector stem. When embedded in the 3′ untranslated region of a reporter gene mRNA, these RNA devices enabled regulation of cis-gene expression by theophylline and guanine by up to 29.5-fold in mammalian cell culture. Furthermore, a NOR logic gate device was constructed by placing two engineered ribozymes in tandem, demonstrating the modularity of the RNA devices. The significant improvement in the regulatory dynamic range (ON/OFF ratio) of the RNA devices based on the HDV ribozyme should provide new opportunities for practical applications.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 684-689 |
| Number of pages | 6 |
| Journal | ACS Synthetic Biology |
| Volume | 2 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 20 2013 |
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Keywords
- aptazyme
- HDV ribozyme
- logic gate
- riboswitch
- ribozyme
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Biomedical Engineering
- Medicine(all)
Cite this
Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes. / Nomura, Yoko; Zhou, Linlin; Miu, Anh; Yokobayashi, Yohei.
In: ACS Synthetic Biology, Vol. 2, No. 12, 20.12.2013, p. 684-689.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes
AU - Nomura, Yoko
AU - Zhou, Linlin
AU - Miu, Anh
AU - Yokobayashi, Yohei
PY - 2013/12/20
Y1 - 2013/12/20
N2 - We engineered small molecule responsive allosteric ribozymes based on the genomic hepatitis delta virus (HDV) ribozyme by replacing the P4-L4 stem-loop with an RNA aptamer through a connector stem. When embedded in the 3′ untranslated region of a reporter gene mRNA, these RNA devices enabled regulation of cis-gene expression by theophylline and guanine by up to 29.5-fold in mammalian cell culture. Furthermore, a NOR logic gate device was constructed by placing two engineered ribozymes in tandem, demonstrating the modularity of the RNA devices. The significant improvement in the regulatory dynamic range (ON/OFF ratio) of the RNA devices based on the HDV ribozyme should provide new opportunities for practical applications.
AB - We engineered small molecule responsive allosteric ribozymes based on the genomic hepatitis delta virus (HDV) ribozyme by replacing the P4-L4 stem-loop with an RNA aptamer through a connector stem. When embedded in the 3′ untranslated region of a reporter gene mRNA, these RNA devices enabled regulation of cis-gene expression by theophylline and guanine by up to 29.5-fold in mammalian cell culture. Furthermore, a NOR logic gate device was constructed by placing two engineered ribozymes in tandem, demonstrating the modularity of the RNA devices. The significant improvement in the regulatory dynamic range (ON/OFF ratio) of the RNA devices based on the HDV ribozyme should provide new opportunities for practical applications.
KW - aptazyme
KW - HDV ribozyme
KW - logic gate
KW - riboswitch
KW - ribozyme
UR - http://www.scopus.com/inward/record.url?scp=84890902769&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890902769&partnerID=8YFLogxK
U2 - 10.1021/sb400037a
DO - 10.1021/sb400037a
M3 - Article
C2 - 23697539
AN - SCOPUS:84890902769
VL - 2
SP - 684
EP - 689
JO - ACS Synthetic Biology
JF - ACS Synthetic Biology
SN - 2161-5063
IS - 12
ER -