Tissue-Specific Stability of Nuclear-and Mitochondrially Encoded mRNAs (original) (raw)

both nuclear-and mitochondrially encoded mRNAs. Steady-state levels of mRNAs encoding mitochon-We have previously shown that the mRNAs encoding drial proteins are drastically different among tissues. subunit VIc (nuclear-encoded) and subunit III (mito-We evaluated tissue-specific variations in mRNA sta-chondrially encoded) are coordinately expressed in var-bility by comparing rates of mRNA decay in liver, ious tissues of the rat possessing a wide range of mito-heart, and muscle following the inhibition of tran-chondrial contents (1). A coordinated expression of scription. Rates of decline of the mRNAs encoding d-these mRNAs may be important for the assembly of aminolevulinate synthase (ALAs), cytochrome c oxi-holoenzyme subunits in a 1:1 stoichiometry (2). Steady-dase subunit VIc (nuclear-encoded), and subunit III state mRNA levels result from a balance between the (mitochondrially encoded) in heart, liver, and muscle rates of mRNA transcription and mRNA degradation. for 6 h following transcription inhibition with actino-Modifications of the mRNA transcript with respect mycin D or ethidium bromide were measured. Subunit to secondary structure, polyadenylation state, or its VIc mRNA levels were least stable in liver (t 1/2 Å 2.4 h), interaction with protein transacting factors are now slightly greater in heart (t 1/2 Å 3.3 h), and very stable recognized as important mechanisms through which in skeletal muscle. Similarly, ALAs mRNA exhibited a changes in mRNA stability could have profound effects t 1/2 of 41 min in liver, but this was markedly increased on tissue mRNA levels (3-5). To date, limited informa-to approximately 11-14 h in heart and skeletal muscle. tion is available on the stability of nuclear-derived (6, 7) In contrast, subunit III was least stable in heart (t 1/2 Å and mitochondrially derived (8-10) mRNAs encoding 2.1 h), somewhat more stable in liver (t 1/2 Å 3.8 h), but proteins destined for the mitochondrion, particularly no decline in subunit III mRNA levels occurred in mus-related to tissue specificity. Large variations in tissue-cle following the inhibition of transcription. Thus, specific rates of mRNA degradation could account for muscle, heart, and liver possess tissue-specific mecha-the difference in steady-state mRNA levels observed nisms which control the stability of mRNAs encoding mitochondrial proteins. In addition, the coordinated between tissues. This study was undertaken to deter-expression of subunit III and VIc mRNAs in different mine if parallelism in the rates of CYTOX mRNA deg-tissues is partly due to parallel rates of mRNA turn-radation could account for the coordinated expression over. This suggests the presence of intra-and extrami-of these mRNAs in different tissues. In addition, since tochondrial factors within a tissue which regulate the heme is an important functional component of the CY-stability of specific mRNAs in a similar manner. ᭧ 1996 TOX holoenzyme, an additional purpose was to evalu-Academic Press, Inc. ate the mRNA stability of the nuclear-encoded enzyme Key Words: cytochrome c oxidase, gene expression, d-aminolevulinate synthase (ALAs), the rate-limiting heme metabolism, mitochondrial biogenesis, mRNA enzyme in heme biosynthesis (11). The half-life (t 1/2) of stability.