title: Long Non-coding RNA BGas Regulates the Cystic Fibrosis Transmembrane Conductance Regulator.
abstract: Cystic fibrosis (CF) is a life-shortening genetic disease. The root cause of CF is heritable recessive mutations that affect the cystic fibrosis transmembrance conductance regulator (CFTR) gene and the subsequent expression and activity of encoded ion channels at the cell surface. We show that CFTR is regulated transcriptionally by the actions of a novel long noncoding RNA (lncRNA), designated as BGas, that emanates from intron 11 of the CFTR gene and is expressed in the antisense orientation relative to the protein coding sense strand. We find that BGas functions in concert with several proteins including HMGA1, HMGB1, and WIBG to modulate the local chromatin and DNA architecture of intron 11 of the CFTR gene and thereby affects transcription. Suppression of BGas or its associated proteins results in a gain of both CFTR expression and chloride ion function. The observations described here highlight a previously underappreciated mechanism of transcriptional control and suggest that BGas may serve as a therapeutic target for specifically activating expression of CFTR.
authors.affiliation: Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Sheena M
authors.initials: SM
authors.lastname: Saayman
authors.affiliation: Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Ackley
authors.affiliation: Biotechnology and Biomedical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Jon
authors.initials: J
authors.lastname: Burdach
authors.affiliation: Biotechnology and Biomedical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Clemson
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Institute for Human Genetics, The University of California San Francisco, San Francisco, California, USA.
authors.forename: Dieter C
authors.initials: DC
authors.lastname: Gruenert
authors.affiliation: Arcturus, Therapeutics, San Diego, California, USA.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Tachikawa
authors.affiliation: Arcturus, Therapeutics, San Diego, California, USA.
authors.forename: Pad
authors.initials: P
authors.lastname: Chivukula
authors.affiliation: Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.|Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, University of the Witwatersrand, WITS 2050, South Africa.|HIV Pathogenesis Research Unit, Department of Molecular Medicine and Haematology, School of Pathology, University of the Witwatersrand, WITS 2050, South Africa.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Weinberg
authors.affiliation: Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.|Biotechnology and Biomedical Sciences, The University of New South Wales, Sydney, Australia.|City of Hope - Beckman Research Institute, Center for Gene Therapy, Duarte, California, USA.
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Morris
mesh_terms: D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D016372:RNA, Antisense / Q000235:genetics*; D062085:RNA, Long Noncoding
chemical_list: D004268:DNA-Binding Proteins; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D019005:Cystic Fibrosis Transmembrane Conductance Regulator