Post-transcriptional regulation of mouse kappa-opioid receptor expression

Three mRNA variants are generated from the mouse kappa-opioid receptor (KOR) gene. The expression patterns of these KOR mRNA variants in adult animal tissues and during developmental stages are examined. Furthermore, the biological significance of generating these variants is demonstrated with respect to two post-transcriptional mechanisms, i.e., mRNA stability and translation efficiency. Variants A and B are both transcribed from promoter 1 of the KOR gene and expressed from early developmental stages through adult life. Although their sequences differ only at a 30-nucleotide insertion for variant B, these two variants are distinct with regard to their expression patterns, mRNA stability, and translation efficiency. Variant A is expressed ubiquitously in all the tissues examined and has a longer t(1/2) (12 h), whereas variant B is more specific to the central nervous system both pre- and postnatally and has a t(1/2) of approximately 8 h. Variant C is transcribed from promoter 2 of the KOR gene and is most specifically expressed, being detected only in the brain stem, spinal cord, and thalamic/hypothalamic areas of postnatal animals. With regard to protein translation, variants B and C are significantly more efficient than variant A. This study provides the evidence for multiple levels of KOR regulation. The biological implication of the generation of KOR mRNA variants is discussed.