Grants and Contracts Details
The ribosome is a large RNA-protein complex that is exclusively responsible for translating messenger RNA into protein. Given this vital role, ribosomes have been thought to function exactly the same way between different cell types. In the past few years, however, evidence has emerged showing heterogeneity in the protein composition of the ribosome, thus leading to the functional specialization of the ribosome. Expression profiling revealed that ribosomal protein L3-like (Rpl3-like) is only expressed in skeletal muscle and the heart; conversely, Rpl3 was highly-expressed in all other tissues surveyed except striated muscle, where it was significantly down-regulated. Given our interest in muscle plasticity, this curious finding prompted us to determine what happens to the expression of Rpl3 and Rpl3-like during skeletal muscle hypertrophy. In response to a hypertrophic stimulus, the expression pattern of these two genes was completely reversed such that Rpl3 was now highly-expressed whereas Rpl3-like was dramatically down-regulated. The objectives of this proposal are: 1) determine the mechanisms regulating the muscle-specific pattern of expression of Rpl3 and Rpl3-like and 2) determine how muscle-specific Rpl3-like alters ribosome function, i.e., specialization of the muscle ribosome. The notion that ribosome specialization occurs in mammals is a very novel and exciting area of research because it represents a completely new level of gene regulation. The fact that there is a muscle-specific Rpl3 strongly suggests ribosomes have become specialized in skeletal muscle – understanding why this is so is the long-term goal of this project. In the short-term, the goal is to better understand the function and regulation of Rpl3-like as the basis for a future R01 grant application investigating the role of ribosome specialization in skeletal muscle plasticity and disease.
|Effective start/end date||9/1/14 → 8/31/17|
- National Institute Arthritis Musculoskeletal & Skin: $361,393.00
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