Knockdown of Muscle-Specific Ribosomal Protein L3-Like Enhances Muscle Function in Healthy and Dystrophic Mice

Betty R Kao, Alberto Malerba, Ngoc B Lu-Nguyen, Pradeep Harish, John J McCarthy, George Dickson, Linda J Popplewell

Research output: Contribution to journalArticlepeer-review

Abstract

Ribosomal protein L3-like (RPL3L) is a poorly characterized ribosomal protein that is exclusively expressed in skeletal and cardiac muscle. RPL3L is also downregulated in Duchenne muscular dystrophy (DMD), suggesting that it may play an important role in muscle biology. In this study, we investigated the role of RPL3L in skeletal muscle of healthy C57 and dystrophic mdx mice. We show that RPL3L is developmentally regulated and that intramuscular adeno-associated virus (AAV)-mediated RPL3L knockdown in the tibialis anterior of C57 and mdx mice results in increased specific force with improved resistance to eccentric contraction induced muscle damage in dystrophic muscles. The mechanism by which RPL3L knockdown improves muscle function remains unclear. Histological observations showed a significant increase in muscle length and decrease in muscle cross-sectional area after RPL3L inhibition suggesting that this ribosomal protein may play a role in myofiber morphology. The endogenous downregulation of RPL3L in DMD may be a protective mechanism that attempts to improve skeletal muscle function and counteract the dystrophic phenotype.

Original languageEnglish
Pages (from-to)457-464
Number of pages8
JournalNucleic Acid Therapeutics
Volume31
Issue number6
DOIs
Publication statusPublished - 10 Dec 2021

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