TISSUE-SPECIFIC STABILITY OF NUCLEAR-ENCODED AND MITOCHONDRIALLY ENCODED MESSENGER-RNAS

Steady-state levels of mRNAs encoding mitochondrial proteins are drast ically different among tissues, We evaluated tissue-specific variation s 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), cytochro me c oxidase subunit VIc (nuclear-encoded), and subunit III (mitochond rially encoded) in heart, liver, and muscle for 6 h following transcri ption inhibition with actinomycin D or ethidium bromide were measured, Subunit VIc mRNA levels were least stable in liver (t(1/2) = 2.4 h), slightly greater in heart t(1/2) = 3.3 h), and very stable in skeletal muscle. Similarly, ALAs mRNA exhibited a tilt of 41 min in liver, but this was markedly increased to approximately 11-14 h in heart and ske letal muscle. In contrast, subunit III was least stable in heart (t(1/ 2) = 2.1 h), somewhat more stable in liver (t(1/2) = 3.8 h), but no de cline in subunit III mRNA levels occurred in muscle following the inhi bition of transcription. Thus, muscle, heart, and liver possess tissue -specific mechanisms which control the stability of mRNAs encoding mit ochondrial proteins. In addition, the coordinated expression of subuni t III and VIc mRNAs in different tissues is partly due to parallel rat es of mRNA turnover. This suggests the presence of intra- and extramit ochondrial factors within a tissue which regulate the stability of spe cific mRNAs in a similar manner. (C) 1996 Academic Press, Inc.