Controlling Mammalian Gene Expression by Allosteric Hepatitis Delta Virus Ribozymes | Zendy

Yoko Nomura | Zendy; Linlin Zhou | Zendy; Anh Miu | Zendy; Yohei Yokobayashi | Zendy

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Controlling Mammalian Gene Expression by Allosteric Hepatitis Delta Virus Ribozymes

Author(s) -

Yoko Nomura,

Linlin Zhou,

Anh Miu,

Yohei Yokobayashi

Publication year - 2013

Publication title -

acs synthetic biology

Language(s) - Uncategorized

Resource type - Journals

SCImago Journal Rank - 2.156

H-Index - 66

ISSN - 2161-5063

DOI - 10.1021/sb400037a

Subject(s) - ribozyme , ligase ribozyme , riboswitch , biology , rna , untranslated region , allosteric regulation , computational biology , gene , aptamer , reporter gene , gene expression , microbiology and biotechnology , virology , genetics , non coding rna , receptor

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.

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