Cell Metabolism
Volume 12, Issue 4, 6 October 2010, Pages 341-351
Journal home page for Cell Metabolism

Article
MicroRNAs Involved in Molecular Circuitries Relevant for the Duchenne Muscular Dystrophy Pathogenesis Are Controlled by the Dystrophin/nNOS Pathway

https://doi.org/10.1016/j.cmet.2010.07.008Get rights and content
Under an Elsevier user license
open archive

Summary

In Duchenne muscular dystrophy (DMD) the absence of dystrophin at the sarcolemma delocalizes and downregulates nitric oxide synthase (nNOS); this alters S-nitrosylation of HDAC2 and its chromatin association. We show that the differential HDAC2 nitrosylation state in Duchenne versus wild-type conditions deregulates the expression of a specific subset of microRNA genes. Several circuitries controlled by the identified microRNAs, such as the one linking miR-1 to the G6PD enzyme and the redox state of cell, or miR-29 to extracellular proteins and the fibrotic process, explain some of the DMD pathogenetic traits. We also show that, at variance with other myomiRs, miR-206 escapes from the dystrophin-nNOS control being produced in activated satellite cells before dystrophin expression; in these cells, it contributes to muscle regeneration through repression of the satellite specific factor, Pax7. We conclude that the pathway activated by dystrophin/nNOS controls several important circuitries increasing the robustness of the muscle differentiation program.

Highlights

► Dystrophin controls gene expression by nNOS relocalization and HDAC2 nitrosylation ► Epigenetic control of miRNA expression is involved in DMD pathogenesis ► miR-1 controls G6PD expression and the redox state of the cell ► miR-206 contributes to satellite cell differentiation by repressing Pax7

HUMDISEASE
DEVBIO
DNA

Cited by (0)

4

These authors contributed equally to this work