Long Non-coding RNA BGas Regulates the Cystic Fibrosis Transmembrane Conductance Regulator

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Saayman, Sheena M
Ackley, Amanda
Burdach, Jon
Clemson, Matthew
Gruenert, Dieter C
Tachikawa, Kiyoshi
Chivukula, Pad
Weinberg, Marc S
Morris, Kevin V
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2016
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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.

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Molecular Therapy

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24

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8

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© 2016 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Biological sciences

Biomedical and clinical sciences

Genetics

Clinical sciences

Medical biotechnology

Science & Technology

Life Sciences & Biomedicine

Biotechnology & Applied Microbiology

Genetics & Heredity

Medicine, Research & Experimental

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Saayman, SM; Ackley, A; Burdach, J; Clemson, M; Gruenert, DC; Tachikawa, K; Chivukula, P; Weinberg, MS; Morris, KV, Long Non-coding RNA BGas Regulates the Cystic Fibrosis Transmembrane Conductance Regulator, Molecular Therapy, 2016, 24 (8), pp. 1351-1357

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