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Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes.

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.

SUBMITTER: Nomura Y

PROVIDER: S-EPMC3874218 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes.

Nomura Yoko Y Zhou Linlin L Miu Anh A Yokobayashi Yohei Y

ACS synthetic biology 20130522 12

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, ...[more]

PMID: 23697539

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