title: Regulation of MAP4K4 gene expression by RNA interference through an engineered theophylline-dependent hepatitis delta virus ribozyme switch.
abstract: Riboswitches are functional non-coding RNA regulatory components that play an important role in the regulation of gene expression in diverse organisms. In particular, using riboswitches to modulate RNA interference (RNAi) enables temporal and spatial control of gene expression in mammalian cells. Herein, a ribozyme gene switch to activate RNAi was fabricated for the artificial regulation of versatile gene silencing through the interaction of an RNA aptamer with small molecules. The device comprised an allosteric HDV ribozyme with an embedded theophylline aptamer and a primary miRNA (pri-miRNA) to silence the MAP4K4 gene in hepatic (HepG2) cells, aiming to achieve dose-dependent control of the activation of RNAi, and then the regulation of the MAP4K4 gene by theophylline. Finally, we demonstrated the feasibility and applicability of utilizing HDV ribozyme switches to activate RNAi for regulating an endogenous gene in mammalian cells.
authors.affiliation: College of Life Sciences, Shanghai University, Shanghai 200444, China and Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Shanghai University, Shanghai 200444, China and Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
authors.forename: Na
authors.initials: N
authors.lastname: Sun
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Shanghai University, Shanghai 200444, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Chen
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
authors.forename: Renjun
authors.initials: R
authors.lastname: Pei
mesh_terms: D002460:Cell Line; D015870:Gene Expression; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005818:Genetic Engineering; D003699:Hepatitis D / Q000235:genetics / Q000821:virology; D003698:Hepatitis Delta Virus / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009690:Nucleic Acid Conformation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D034622:RNA Interference / Q000187:drug effects; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics*; D058928:Riboswitch; D013806:Theophylline / Q000494:pharmacology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D016337:RNA, Catalytic; D058928:Riboswitch; D013806:Theophylline; C117090:MAP4K4 protein, human; D017346:Protein Serine-Threonine Kinases