Navigation Links
Gene network restores CF protein function

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 amount of the protein that is transported to the cell membrane where it functions as an ion channel.

"We first wanted to determine how this gene network impacts the CFTR protein produced in people who don't have cystic fibrosis," says lead author Shyam Ramachandran, Ph.D.. "We identified a novel regulatory circuit, but then asked ourselves if any of this affected the mutant protein."

Surprisingly, the researchers found that when the gene network was activated by miR-138, it not only increased the amount of the mutated protein, but also partially restored the protein's function.

By manipulating the microRNA network, the UI team was able to change the fate of the misfolded CFTR from being degraded in the cell to functioning as an ion channel in the cell membrane.

"This was a very surprising finding," Ramachandran says. "It unexpectedly helps rescue the function of the mutant protein."

Because most people with CF have one or two copies of the delta F508 mutation, interventions that overcome the CFTR protein-processing problems caused by this mutation might have important implications for new ways of treating CF.

"In the field of CF therapeutics there's great interest in identifying ways to restore the function of this misprocessed protein," McCray says. "We were very surprised that manipulating this microRNA regulated gene network had this rescuing effect. This opens up a new avenue for the development of CF therapies."

Contact: Molly Rossiter
University of Iowa Health Care

Related biology news :

1. Frog calls inspire a new algorithm for wireless networks
2. Service Credit Union Selects DigitalPersona to Secure Access to Network and Applications
3. Penn researchers improve living tissues with 3-D printed vascular networks made from sugar
4. UC Berkeley chemists installing first carbon dioxide sensor network in Oakland
5. Manipulation of a specific neural circuit buried in complicated brain networks in primates
6. Scientists tie DNA repair to key cell signaling network
7. A network of knowledge on biodiversity and ecosystem services in Europe
8. Minneapolis Heart Institute selected to participate in Cardiovascular Cell Therapy Research Network
9. Activity in brain networks related to features of depression
10. Building the European Unions Natura 2000 -- the largest ever network of protected areas
11. Study demonstrates cells can acquire new functions through transcriptional regulatory network
Post Your Comments:
(Date:6/9/2016)... Finland , June 9, 2016 ... National Police deploy Teleste,s video security solution to ensure the ... France during the major tournament ... data communications systems and services, announced today that its video ... Prefecture to back up public safety across the ...
(Date:6/2/2016)... 2016 The Department of Transport Management ... 44 million US Dollar project, for the , ... Personalization, Enrolment, and IT Infrastructure , to ... and implementation of Identity Management Solutions. Numerous renowned international vendors ... Decatur was selected for the most compliant and ...
(Date:6/1/2016)... , June 1, 2016 ... in Election Administration and Criminal Identification to Boost Global ... a recently released TechSci Research report, " Global Biometrics ... Region, Competition Forecast and Opportunities, 2011 - 2021", the ... billion by 2021, on account of growing security concerns ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... June 27, 2016   Ginkgo Bioworks , a ... engineering, was today awarded as one of the ... the world,s most innovative companies. Ginkgo Bioworks is ... the real world in the nutrition, health and ... directly with customers including Fortune 500 companies to ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... Researchers at ... most commonly-identified miRNAs in people with peritoneal or pleural mesothelioma. Their findings are the ... read it now. , Diagnostic biomarkers are signposts in the blood, lung fluid ...
(Date:6/23/2016)... , June 23, 2016 /PRNewswire/ - FACIT has ... Ontario biotechnology company, Propellon Therapeutics Inc. ... and commercialization of a portfolio of first-in-class WDR5 ... targets such as WDR5 represent an exciting class ... in precision medicine for cancer patients. Substantial advances ...
(Date:6/23/2016)... SANTA MONICA, Calif. , June 23, 2016  The Prostate Cancer ... to pioneer increasingly precise treatments and faster cures for prostate cancer. Members of ... 77 institutions across 15 countries. Read More About the ... ... ...
Breaking Biology Technology: