Browsing by Subject "OVER-EXPRESSION"

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  • Olsen, Rikke K. J.; Konarikova, Eliska; Giancaspero, Teresa A.; Mosegaard, Signe; Boczonadi, Veronika; Matakovic, Lavinija; Veauville-Merllie, Alice; Terrile, Caterina; Schwarzmayr, Thomas; Haack, Tobias B.; Auranen, Mari; Leone, Piero; Galluccio, Michele; Imbard, Apolline; Gutierrez-Rios, Purificacion; Palmfeldt, Johan; Graf, Elisabeth; Vianey-Saban, Christine; Oppenheim, Marcus; Schiff, Manuel; Pichard, Samia; Rigal, Odile; Pyle, Angela; Chinnery, Patrick F.; Konstantopoulou, Vassiliki; Moslinger, Dorothea; Feichtinger, Rene G.; Talim, Beril; Topaloglu, Haluk; Coskun, Turgay; Gucer, Safak; Botta, Annalisa; Pegoraro, Elena; Malena, Adriana; Vergani, Lodovica; Mazza, Daniela; Zollino, Marcella; Ghezzi, Daniele; Acquaviva, Cecile; Tyni, Tiina; Boneh, Avihu; Meitinger, Thomas; Strom, Tim M.; Gregersen, Niels; Mayr, Johannes A.; Horvath, Rita; Barile, Maria; Prokisch, Holger (2016)
    Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and a neuromuscular phenotype. Despite recent advances in understanding the genetic basis of MADD, a number of cases remain unexplained. Here, we report clinically relevant variants in FLAD1, which encodes FAD synthase (FADS), as the cause of MADD and respiratory-chain dysfunction in nine individuals recruited from metabolic centers in six countries. In most individuals, we identified biallelic frameshift variants in the molybdopterin binding (MPTb) domain, located upstream of the FADS domain. Inasmuch as FADS is essential for cellular supply of FAD cofactors, the finding of biallelic frameshift variants was unexpected. Using RNA sequencing analysis combined with protein mass spectrometry, we discovered FLAD1 isoforms, which only encode the FADS domain. The existence of these isoforms might explain why affected individuals with biallelic FLAD1 frameshift variants still harbor substantial FADS activity. Another group of individuals with a milder phenotype responsive to riboflavin were shown to have single amino acid changes in the FADS domain. When produced in E. coli, these mutant FADS proteins resulted in impaired but detectable FADS activity; for one of the variant proteins, the addition of FAD significantly improved protein stability, arguing for a chaperone-like action similar to what has been reported in other riboflavin-responsive inborn errors of metabolism. In conclusion, our studies identify FLAD1 variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD and shed light on the mechanisms by which FADS ensures cellular FAD homeostasis.
  • Abdullah; Faraji, Sahar; Mehmood, Furrukh; Malik, Hafiz Muhammad Talha; Ahmed, Ibrar; Heidari, Parviz; Poczai, Péter (2021)
    The gibberellic acid-stimulated Arabidopsis (GASA/GAST) gene family is widely distributed in plants and involved in various physiological and biological processes. These genes also provide resistance to abiotic and biotic stresses, including antimicrobial, antiviral, and antifungal. We are interested in characterizing the GASA gene family and determining its role in various physiological and biological process in Theobroma cacao. Here, we report 17 tcGASA genes distributed on six chromosomes in T. cacao. The gene structure, promoter region, protein structure and biochemical properties, expression, and phylogenetics of all tcGASAs were analyzed. Phylogenetic analyses divided tcGASA proteins into five groups. Among 17 tcGASA genes, nine segmentally duplicating genes were identified which formed four pairs and cluster together in phylogenetic tree. Differential expression analyses revealed that most of the tcGASA genes showed elevated expression in the seeds (cacao food), implying their role in seed development. The differential expression of tcGASAs was recorded between the tolerant and susceptible cultivars of cacao, which indicating their possible role as fungal resistant. Our findings provide new insight into the function, evolution, and regulatory system of the GASA family genes in T. cacao and may suggest new target genes for development of fungi-resistant cacao varieties in breeding programs.