Role of Inhibition of Long Intergenic Non-coding RNA-p21 on Contractility, Skeletal Muscle Metabolism and Physical Performance

• Grant number: 24/03110-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2024
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Tiago Fernandes
• Grantee: Mateus José Arruda
• Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/03138-2 - Functions and regulatory mechanisms of lincRNA-p21 in skeletal muscle: role on stem cell fate, myogenesis, trophism, contractility, exercise performance and injury repair, AP.PNGP.PI

Abstract

Skeletal muscle has vital functions in the body and high plasticity under physiological and pathological conditions. Therefore, the identification of new mechanisms that control phenotypic adaptation processes can contribute to the understanding of muscle biology and potentially allow the identification of new therapeutic targets. The discovery that 98% of the human genome, although transcribed, does not encode proteins was crucial to recognizing the role of long non-coding RNAs (lncRNAs) as critical regulators of cellular function at the epigenetic, transcriptional, and post-transcriptional level. Although studies indicate that lncRNAs play key roles in tissue structure and function, their role in controlling muscle mass and other phenotypic adaptations remains little known. lincRNA-p21 is involved in diverse cellular processes via regulating the expression of multiple target genes; however, its role in skeletal muscle is unknown. Therefore, the main objective of this study is to investigate the impact of lincRNA-p21 deletion on myogenic, phenotypic, functional, reparative and molecular adaptations of skeletal muscle; and provide additional knowledge about how transcriptional and post-transcriptional processes are integrated to orchestrate these muscle changes. We will evaluate the effects of lincRNA-p21 inhibition on contractility, metabolism and muscle regeneration, as well as its effects on physical performance. Thus, the study of lincRNA-p21 may lead to the identification of molecular circuits that are controlled by RNAs (lncRNA-miRNA-mRNA network) during the process of skeletal muscle differentiation and that, when deregulated, lead to pathological events. These discoveries will provide insights that can assist in understanding many basic concepts of the molecular mechanisms involved in skeletal muscle homeostasis and in the development of new therapeutic interventions for muscle diseases.