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RNA subunit of mitochondrial RNA-processing enzyme is induced by contractile activity in striated muscle
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8573.
Abstract:
A small RNA encoded within the nucleus of yeast and mammalian cells is an essential subunit of a mitochondrial RNA-processing endonuclease (RNase MRP) that generates primers for mitochondrial DNA (mtDNA) replication. We examined expression of MRP-RNA in specialized subtypes of mammalian striated muscles that differ markedly in respiratory activity and in muscles subjected to chronic stimulation via the motor nerve, a potent stimulus to mitochondrial biogenesis. MRP-RNA was more abundant in mitochondria-rich cardiac and slow-twitch skeletal muscles than in glycolytic fast-twitch skeletal muscles. Forced contractile activity resulting from nerve stimulation increased expression of MRP-RNA by 3.5-fold within the first day and by 14-fold within 14 days. Changes in abundance of MRP-RNA preceded but otherwise occurred in parallel to changes in specific activity of citrate synthase, a marker of mitochondrial proliferation shown previously to correlate with mtDNA copy number in this model. Another small RNA (U1) also was induced transiently (1-3 days) by nerve stimulation, but such changes were not sustained and were of less magnitude (< 4-fold) than changes in MRP-RNA. These findings are consistent with the hypothesis that MRP-RNA may have a regulatory function with respect to mtDNA replication and mitochondrial biogenesis.
Insights
Mitochondrial RNA processing and 1 (MRP-RNA) is more abundant in energy-demanding muscles. Nerve stimulation significantly increases MRP-RNA, suggesting a role in mitochondrial DNA replication and biogenesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Mitochondrial RNA processing and 1 (MRP-RNA) is a key component of RNase MRP, essential for mitochondrial DNA (mtDNA) replication.
- MRP-RNA is encoded in the nucleus and functions within mitochondria.
Purpose of the Study:
- To investigate the expression of MRP-RNA in different mammalian striated muscle subtypes.
- To determine the effect of chronic nerve stimulation on MRP-RNA expression, a known stimulus for mitochondrial biogenesis.
Main Methods:
- Quantitative analysis of MRP-RNA abundance in cardiac, slow-twitch skeletal, and fast-twitch skeletal muscles.
- Assessment of MRP-RNA levels in muscles subjected to chronic motor nerve stimulation.
- Measurement of citrate synthase activity as a marker for mitochondrial proliferation.
Main Results:
- MRP-RNA was more abundant in mitochondria-rich muscles (cardiac, slow-twitch) compared to glycolytic muscles (fast-twitch).
- Nerve stimulation led to a rapid and sustained increase in MRP-RNA expression (3.5-fold at day 1, 14-fold at day 14).
- Changes in MRP-RNA preceded and paralleled increases in citrate synthase activity.
Conclusions:
- MRP-RNA expression is higher in muscles with greater respiratory demands.
- MRP-RNA levels are significantly upregulated by chronic nerve stimulation, indicating a role in mitochondrial biogenesis.
- Findings support the hypothesis that MRP-RNA regulates mtDNA replication and mitochondrial proliferation.