title: miRNA let-7 expression is regulated by glucose and TNF-α by a remote upstream promoter.
abstract: miRNAs regulate protein abundance and control diverse aspects of cellular processes and biological functions in metabolic diseases, such as obesity and type 2 diabetes (T2D). Let (lethal)-7 miRNAs specifically targets genes associated with T2D and have been implicated in the regulation of peripheral glucose metabolism, yet the direct regulators of let-7 miRNA expression are unknown. In the present study, we report on a putative promoter region for the let-7a-1, let-7f-1 and let-7d gene cluster on chromosome 9 and characterize the promoter activity of this novel area. We show that promoter activity and let-7 miRNA expression is dynamically regulated in response to different factors including serum, glucose, tumour necrosis factor (TNF)-α and caffeine. These findings will contribute to understanding the interaction between precise promoter elements to control the transcription and translation of let-7 miRNA genes.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Katayama
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Rasmus J O
authors.initials: RJ
authors.lastname: Sjögren
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Brendan
authors.initials: B
authors.lastname: Egan
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden Anna.Krook@ki.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Krook
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002110:Caffeine / Q000378:metabolism*; D002478:Cells, Cultured; D002899:Chromosomes, Human, Pair 9; D019295:Computational Biology; D030561:Databases, Nucleic Acid; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D015894:Genome, Human; D005947:Glucose / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism; D035683:MicroRNAs / Q000819:agonists* / Q000378:metabolism; D005810:Multigene Family; D009994:Osmolar Concentration; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D035683:MicroRNAs; D012333:RNA, Messenger; D011994:Recombinant Proteins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C487931:mirnlet7 microRNA, human; D002110:Caffeine; D005947:Glucose
keywords: gene expression; microRNA (micro ribonucleic acid); promoter regulation; transcription factor; type 2 diabetes