RESUMO
AU-rich elements (AREs) comprise one of the most widely studied families of regulatory RNA structures met in RNAs engaged in complex immunological reactions. A multitude of genetic, molecular, holistic and functional studies have been utilized for the analyses of the AREs and their interactions to proteins that bind to them. Data stemming from these studies brought forth a world of RNA-related check-points against infection, chronic inflammation, tumor associated immunity, and autoimmunity; and the interest to capitalize the interactions of AREs for clinical management and therapy. They also provided lessons on the cellular capabilities of post-transcriptional control. Originally thought as transcript-restricted regulators of turnover and translation, ARE-binding proteins do in fact harbor great versatility and interactivity across nuclear and cytoplasmic compartments; and act as functional coordinators of immune-cellular programs. Harnessing these deterministic functions requires extensive knowledge of their synergies or antagonisms at a cell-specific level; but holds great promise since it can provide the efficacy of combinatorial therapies with single agents.
Assuntos
Elementos Ricos em Adenilato e Uridilato/efeitos dos fármacos , Doenças Autoimunes/imunologia , Regulação da Expressão Gênica/imunologia , Proteínas de Ligação a RNA/imunologia , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Doenças Autoimunes/terapia , Doença Crônica , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Inflamação/terapia , Proteínas de Ligação a RNA/genéticaRESUMO
Histone acetylation is directly related to gene expression. In yeast, the acetyltransferase general control nonderepressible-5 (GCN5) targets histone H3 and associates with transcriptional co-activators alteration/deficiency in activation-2 (ADA2) and alteration/deficiency in activation-3 (ADA3) in complexes like SAGA. Arabidopsis thaliana has two genes encoding proteins, designated ADA3a and ADA3b, that correspond to yeast ADA3. We investigated the role of ADA3a and ADA3b in regulating gene expression during flowering time. Specifically, we found that knock out mutants ada3a-2 and the double mutant ada3a-2 ada3b-2 lead to early flowering compared to the wild type plants under long day (LD) conditions and after moving plants from short days to LD. Consistent with ADA3a being a repressor of floral initiation, FLOWERING LOCUS T (FT) expression was increased in ada3a mutants. In contrast, other genes involved in multiple pathways leading to floral transition, including FT repressors, players in GA signaling, and members of the SPL transcriptional factors, displayed reduced expression. Chromatin immunoprecipitation analysis revealed that ADA3a affects the histone H3K14 acetylation levels in SPL3, SPL5, RGA, GAI, and SMZ loci. In conclusion, ADA3a is involved in floral induction through a GCN5-containing complex that acetylates histone H3 in the chromatin of flowering related genes.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Flores/fisiologia , Proteínas Nucleares/metabolismo , Transcrição Gênica , Acetilação , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , DNA Bacteriano/genética , Epistasia Genética , Flores/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Histonas/metabolismo , Mutação/genética , Proteínas Nucleares/química , Proteínas Nucleares/genética , Fenótipo , Filogenia , Ligação Proteica , Domínios Proteicos , Homologia de Sequência de Aminoácidos , Fatores de TempoRESUMO
Chios mastic products are well-known for their broad applications in food industry, cosmetics, and healthcare since the antiquity. Given our recent finding that Chios mastic water (CMW) exerts antigenotoxic action, in the present study, we evaluated the genotoxic as well as the antigenotoxic potential of the four major compounds of CMW, namely, verbenone, α-terpineol, linalool, and trans-pinocarveol. The cytokinesis block micronucleus (CBMN) assay in cultured human lymphocytes and the Drosophila Somatic Mutation And Recombination Test (SMART), also known as the wing spot test, were employed. None of the four major CMW's constituents or their mixtures showed genotoxic or recombinogenic activity in either of the assays used. Co-treatment of each of the constituents with MMC revealed that all except trans-pinocarveol exerted antigenotoxic potential. Moreover, co-administration of verbenone with linalool or α-terpineol presented statistically significant reduction of MMC-induced mutagenicity. In conclusion, the major CMW constituents were shown to be free of genotoxic effects, while some exerted antigenotoxic activity either alone or in combinations, suggesting synergistic phenomena. Our results provide evidence on the key antigenotoxicity effectors of the plant extract CMW.