Emerging Role for Linear and Circular Spermine Oxidase RNAs in Skeletal Muscle Physiopathology.

Abstract

Skeletal muscle atrophy is a pathological condition so far without effective treatment and poorly understood at a molecular level. Emerging evidence suggest a key role for circular RNAs (circRNA) during myogenesis and their deregulation has been reported to be associated with muscle diseases. Spermine oxidase (SMOX), a polyamine catabolic enzyme plays a critical role in muscle differentiation and the existence of a circRNA arising from SMOX gene has been recently identified. In this study, we evaluated the expression profile of circular and linear SMOX in both C2C12 differentiation and dexamethasone-induced myotubes atrophy. To validate our findings in vivo their expression levels were also tested in two murine models of amyotrophic lateral sclerosis: SOD1G93A and hFUS+/+, characterized by progressive muscle atrophy. During C2C12 differentiation, linear and circular SMOX show the same trend of expression. Interestingly, in atrophy circSMOX levels significantly increased compared to the physiological state, in both in vitro and in vivo models. Our study demonstrates that SMOX represents a new player in muscle physiopathology and provides a scientific basis for further investigation on circSMOX RNA as a possible new therapeutic target for the treatment of muscle atrophy.

• Authors: Jonathan Fernando Reinoso-Sánchez, Giulia Baroli, Guglielmo Duranti, Silvia Scaricamazza, Stefania Sabatini, Cristiana Valle, Mariangela Morlando, Robert Anthony Casero Jr, Irene Bozzoni, Paolo Mariottini, Roberta Ceci, Manuela Cervelli
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 21 (Nov 03 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33153123 (Publication Type: Journal Article)

Chemical References

• FUS protein, mouse
• RNA, Circular
• RNA, Messenger
• RNA, Untranslated
• RNA-Binding Protein FUS
• Sod1 protein, mouse
• Superoxide Dismutase-1
• Oxidoreductases Acting on CH-NH Group Donors

Topics

• Amyotrophic Lateral Sclerosis (genetics, metabolism, pathology)
• Animals
• Cell Differentiation (genetics)
• Cells, Cultured
• Disease Models, Animal
• Female
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Muscle Fibers, Skeletal (pathology, physiology)
• Muscle, Skeletal (metabolism, pathology)
• Muscular Atrophy (genetics, metabolism, pathology)
• Oxidoreductases Acting on CH-NH Group Donors (genetics, physiology)
• RNA, Circular (physiology)
• RNA, Messenger (physiology)
• RNA, Untranslated (physiology)
• RNA-Binding Protein FUS (genetics)
• Superoxide Dismutase-1 (genetics)
• Polyamine Oxidase