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The mRNA stability of regulators of mitochondrial biogenesis is inversely related to muscle oxidative capacity
Author(s) -
D'souza Donna M.,
Lai Ruanne Y.,
Hood David A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1105.5
Subject(s) - mitochondrial biogenesis , oxidative phosphorylation , biogenesis , microbiology and biotechnology , messenger rna , chemistry , mitochondrion , biology , biochemistry , gene
The stabilization of mRNA permits a greater amount of mRNA to be translated into protein. Accordingly, the mRNA stability of nuclear genes encoding mitochondrial proteins may be an important regulatory pathway in striated muscle mitochondrial biogenesis. We hypothesized that the transcript stability of these genes is highly regulated in oxidative tissue, prompting rapid rates of mRNA turnover. The stability of nuclear‐encoded mitochondrial transcription factor A (Tfam) and nuclear respiratory factor 2 (NRF‐2) was assessed in extracts of fast‐twitch white (FTW), fast‐twitch red (FTR), slow‐twitch red (STR) and heart muscle using in vitro decay assays. mRNA decay rates were highest in oxidative tissue, as evident by the 2.4‐fold and 3.6‐fold lower half‐life for Tfam and NRF‐2, respectively, in heart compared to low oxidative FTW muscle. This corresponded well to the high ratio of destabilizing:stabilizing RNA binding protein expression (AUF1 p42:HuR) found in heart muscle. Additionally, there was a greater abundance of the destabilizing GRE‐binding protein CUGBP1 in cardiac tissue. These values parallel the observed rates of transcript decay. Thus, the half‐lives of mRNAs encoding mitochondrial biogenesis regulator proteins are inversely related to oxidative capacity, and provide an additional means for the regulation of mitochondrial transcripts in oxidative tissue.