title: Upregulating endogenous genes by an RNA-programmable artificial transactivator.
abstract: To promote expression of endogenous genes ad libitum, we developed a novel, programmable transcription factor prototype. Kept together via an MS2 coat protein/RNA interface, it includes a fixed, polypeptidic transactivating domain and a variable RNA domain that recognizes the desired gene. Thanks to this device, we specifically upregulated five genes, in cell lines and primary cultures of murine pallial precursors. Gene upregulation was small, however sufficient to robustly inhibit neuronal differentiation. The transactivator interacted with target gene chromatin via its RNA cofactor. Its activity was restricted to cells in which the target gene is normally transcribed. Our device might be useful for specific applications. However for this purpose, it will require an improvement of its transactivation power as well as a better characterization of its target specificity and mechanism of action.
authors.affiliation: Laboratory of Cerebral Cortex Development, SISSA, Trieste, 34136, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fimiani
authors.affiliation: Laboratory of Cerebral Cortex Development, SISSA, Trieste, 34136, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Goina
authors.affiliation: Laboratory of Cerebral Cortex Development, SISSA, Trieste, 34136, Italy amallama@sissa.it.
authors.forename: Antonello
authors.initials: A
authors.lastname: Mallamaci
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D015534:Trans-Activators; D012313:RNA