alexa IRES-mediated translation of utrophin A is enhanced by glucocorticoid treatment in skeletal muscle cells.
Chemistry

Chemistry

Journal of Physical Chemistry & Biophysics

Author(s): Miura P, Andrews M, Holcik M, Jasmin BJ

Abstract Share this page

Abstract Glucocorticoids are currently the only drug treatment recognized to benefit Duchenne muscular dystrophy (DMD) patients. The nature of the mechanisms underlying the beneficial effects remains incompletely understood but may involve an increase in the expression of utrophin. Here, we show that treatment of myotubes with 6alpha-methylprednisolone-21 sodium succinate (PDN) results in enhanced expression of utrophin A without concomitant increases in mRNA levels thereby suggesting that translational regulation contributes to the increase. In agreement with this, we show that PDN treatment of cells transfected with monocistronic reporter constructs harbouring the utrophin A 5'UTR, causes an increase in reporter protein expression while leaving levels of reporter mRNAs unchanged. Using bicistronic reporter assays, we further demonstrate that PDN enhances activity of an Internal Ribosome Entry Site (IRES) located within the utrophin A 5'UTR. Analysis of polysomes demonstrate that PDN causes an overall reduction in polysome-associated mRNAs indicating that global translation rates are depressed under these conditions. Importantly, PDN causes an increase in the polysome association of endogenous utrophin A mRNAs and reporter mRNAs harbouring the utrophin A 5'UTR. Additional experiments identified a distinct region within the utrophin A 5'UTR that contains the inducible IRES activity. Together, these studies demonstrate that a translational regulatory mechanism involving increased IRES activation mediates, at least partially, the enhanced expression of utrophin A in muscle cells treated with glucocorticoids. Targeting the utrophin A IRES may thus offer an important and novel therapeutic avenue for developing drugs appropriate for DMD patients.
This article was published in PLoS One and referenced in Journal of Physical Chemistry & Biophysics

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 2nd International Conference on Physics
    Aug 28-30, 2017 Brussels, Belgium
  • 5th Global Chemistry Congress
    September 04-06, 2017 London, UK
  • 3rd World Chemistry Conference
    September 11-12, 2017 Dallas, USA
  • Global Conference on Physical Chemistry
    September 18-19, 2017 Dublin, Ireland
  • 2nd International Conference on Applied Chemistry  
    October 16-17, 2017 Toronto, Canada
Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords