New CNS dystrophins uncovered by RNA-Seq.

The DMD gene, mutated in Duchenne muscular dystrophy (DMD) patients, encodes a group of proteins, the dystrophins, which are produced from multiple promoters and alternative splicing events in the brain and retina. Dystrophins are expressed in different neural cell types; their absence alters several cellular pathways responsible for central comorbidities in DMD. However, the specific cellular expression of dystrophins in the central nervous system (CNS) is still poorly understood. In an article published in Human Molecular Genetics, Cyrille Vaillend and Jérôme Roger (Institut des Neurosciences Paris-Saclay – NeuroPSI, CNRS/UPSaclay, Orsay), in collaboration with a Mexican team (C Montanez, CINVESTAV, Mexico city), have studied the transcriptional regulation of the DMD gene in the brain and retina, in the framework of a French-Mexican scientific cooperation programme (EcosNord, Université Sorbonne Paris Nord).
This study provides a first RNA-Seq reference showing the differential expression of dystrophins, their splice variants and associated proteins in different cell types and at different stages of CNS maturation in mice. New splicing events affecting several dystrophins were also identified, including a new in-frame exon within intron 51 (E51b) and inclusions of intronic sequence with stop codons that lead to the presence of truncated proteins lacking their C-terminus. The expression of these new dystrophins, N-Dp427 and N-Dp260, was validated. This study thus brings to light a series of important new findings for understanding the neurobiology of DMD.

Tissue- and cell-specific whole-transcriptome meta-analysis from brain and retina reveals differential expression of dystrophin complexes and new dystrophin spliced isoforms. César García-Cruz, Jorge Aragón, Sophie Lourdel, Ahrmad Annan, Jérôme E Roger, Cecilia Montanez, Cyrille Vaillend.

Article published in Human Molecular GeneticsAccess to the manuscript