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Gene network restores CF protein function
Date:8/1/2012

Researchers at the University of Iowa Carver College of Medicine have discovered a genetic process that can restore function to a defective protein, which is the most common cause of cystic fibrosis (CF).

Cystic fibrosis is an inherited disease caused by mutations in a gene that adversely affect its protein product. In its correct form and cellular location, this protein, cystic fibrosis transmembrane conductance regulator (CFTR), functions as a channel for ions to move across cell membranes, and is critical for maintaining cellular salt and water balance.

The most common CF-causing genetic mutation, known as delta F508, disrupts the process whereby the CFTR protein is folded into its correct shape and shipped to the membranes of cells that line the airways and other organs. Most of the defective CFTR protein is misprocessed and gets degraded. The lack of normal CFTR ion channels leads to numerous problems, including lung infection and inflammation, the major causes of disease and death in cystic fibrosis.

Despite its importance, how the CFTR protein is made and delivered to cell membranes in its functioning form is not well understood. The UI team led by Paul McCray, M.D., professor of pediatrics and microbiology with UI Health Care and the Roy J. Carver Chair in Pulmonary Research and Vice Chair for Research in Pediatrics, investigated the role of microRNAs -- small non-coding stretches of RNA -- in regulating expression of CFTR.

In their research, McCray and colleagues discovered that one particular microRNA, called miR-138, helps control the biosynthesis of CFTR by regulating a network of genes involved in the production and processing of the protein. The study, published online the week of July 30 in the Proceedings of the National Academy of Sciences (PNAS) Early Edition, shows that that miR-138 acts on the other genes to orchestrate a cellular program that increases production of CFTR and increases the am
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Contact: Molly Rossiter
molly-rossiter@uiowa.edu
319-356-7127
University of Iowa Health Care
Source:Eurekalert

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