Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy

Chiara Scotton, Matteo Bovolenta, Elena Schwartz, Maria Sofia Falzarano, Elena Martoni, Chiara Passarelli, Annarita Armaroli, Hana Osman, Carmelo Rodolico, Sonia Messina, Elena Pegoraro, Adele D'Amico, Enrico Bertini, Francesca Gualandi, Marcella Neri, Rita Selvatici, Patrizia Boffi, Maria Antonietta Maioli, Hanns Lochmüller, Volker StraubKatherine Bushby, Tiziana Castrignanò, Graziano Pesole, Patrizia Sabatelli, Luciano Merlini, Paola Braghetta, Paolo Bonaldo, Paolo Bernardi, Reghan Foley, Sebahattin Cirak, Irina Zaharieva, Francesco Muntoni, Daniele Capitanio, Cecilia Gelfi, Ekaterina Kotelnikova, Anton Yuryev, Michael Lebowitz, Xiping Zhang, Brian A. Hodge, Karyn A. Esser, Alessandra Ferlini

Research output: Contribution to journalArticlepeer-review


Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1-/-) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in both Col6a1-/- mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly, Bmal1-/- (also known as Arntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes.The involvement of circadian rhythms in collagenVImyopathies is new and links autophagy and mitochondrial abnormalities. It also opens newavenues for therapies of hereditary myopathies tomodulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis.

Original languageEnglish
Pages (from-to)1671-1684
Number of pages14
JournalJournal of Cell Science
Issue number8
Publication statusPublished - Apr 1 2016


  • Circadian rhythms
  • Interactome pathway
  • Myopathies
  • RNAseq

ASJC Scopus subject areas

  • Cell Biology


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