Tissue-specific stability of nuclear- and mitochondrially encoded mRNAs.
Steady-state levels of mRNAs encoding mitochondrial proteins are drastically different among tissues. We evaluated tissue-specific variations in mRNA stability by comparing rates of mRNA decay in liver, heart, and muscle following the inhibition of transcription. Rates of decline of the mRNAs encoding delta-aminolevulinate synthase (ALAs), cytochrome c oxidase subunit VIc (nuclear-encoded), and subunit III (mitochondrially encoded) in heart, liver, and muscle for 6 h following transcription inhibition with actinomycin D or ethidium bromide were measured. Subunit VIc mRNA levels were least stable in liver (t1/2 = 2.4 h), slightly greater in heart (t1/2 = 3.3 h), and very stable in skeletal muscle. Similarly, ALAs mRNA exhibited a t1/2 of 41 min in liver, but this was markedly increased to approximately 11-14 h in heart and skeletal muscle. In contrast, subunit III was least stable in heart (t1/2 = 2.1 h), somewhat more stable in liver (t1/2 = 3.8 h), but no decline in subunit III mRNA levels occurred in muscle following the inhibition of transcription. Thus, muscle, heart, and liver possess tissue-specific mechanisms which control the stability of mRNAs encoding mitochondrial proteins. In addition, the coordinated expression of subunit III and VIc mRNAs is different tissues is partly due to parallel rates of mRNA turnover. This suggests the presence of intra- and extramitochondrial factors within a tissue which regulate the stability of specific mRNAs in a similar manner.
Connor
M K
MK
Department of Biology, York University, Ontario, Canada. dhood@yorku.ca
Takahashi
M
M
Hood
D A
DA
D000624:5-Aminolevulinate Synthetase / Q000235:genetics; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004355:Drug Stability; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014158:Transcription, Genetic / Q000187:drug effects
D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D003609:Dactinomycin; D003576:Electron Transport Complex IV; D000624:5-Aminolevulinate Synthetase; D002950:Citrate (si)-Synthase