Grants and Contracts Details
Project Summary/Abstract Striated muscle tissue contains the highest mitochondrial content and the largest known proteins, which present unique challenges to the translational machinery. Muscle tissue specifically expresses a paralogous ribosomal protein, RLP3L, that is roughly 80% similar to the ubiquitous RPL3, which is essential to the formation of the large subunit of the ribosome. In muscle, RPL3L substitutes for RPL3 in the ribosome, but how this alters ribosome function remains unknown. Furthermore, these two paralogs demonstrate an inverse relationship under conditions of muscle adaptation, stress, and pathology. In dystrophic muscle, RPL3L is lost in favor of RPL3 in the ribosome, but the effects on muscle functional decline are not understood. Recent evidence suggests that ribosomes can specialize in order to selectively translate certain genes into proteins. Additionally, translation control has emerged as a novel layer of regulation for mitochondrial function. Taken together, the loss of RPL3L in dystrophic muscle impairs ribosome specialization, thus contributes to an imbalance between mitochondrial and sarcomeric protein synthesis. Rescue of the muscle specific ribosomal protein in muscular dystrophy will provide the first evidence for a role of ribosome specialization in muscle functional decline. The proposed studies will also, for the first time, investigate the impact of glucocorticoids on muscle ribosome specialization and translational selectivity. Successful completion of the proposed studies will reveal new therapeutic targets as well novel mechanisms underlying the pathophysiology of chronic debilitating diseases.
|Effective start/end date||8/17/22 → 7/31/24|
- National Institute Arthritis Musculoskeletal & Skin: $116,970.00
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