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A nearly full length ME cDNA has been obtained and sequenced. The identity has been established by comparison of the translated nucleotide sequence with the amino acid sequence of 7 tryptic peptides from purified ME. Northern analysis with this cDNA shows that ME mRNA consists of two different messages of about 27S and 21S. The size difference between two ME mRNAs (approximately equal to 27S and 21S) is attributed to the differences in the 3' noncoding regions. The relative ratios of the two ME mRNAs differ in various tissues examined (liver, heart, kidney, brain, lung, spleen, and testis). Their regulation by T3 is tissue specific with coordinate stimulation of both mRNAs in liver, heart and kidney, suggesting a single promoter for both mRNAs and no stimulation of either in the other tissues. T3 regulates ME mRNA synthesis via a dual-tissue specific mechanism by increasing the rate of transcription in liver and heart and stabilizing nuclear ME RNA sequences only in liver.