Regulatory role of the 3 ' untranslated region of luteinizing hormone receptor: effect on mRNA stability

Posttranscriptional regulation of luteinizing hormone receptor (LHR) mRNA h as a significant role in regulating cell surface receptor expression during ovarian cycle. In order to gain insight into the mechanism of posttranscri ptional regulation, the eis-acting elements in the 3' untranslated region ( 3' UTR) of LHR mRNA were examined by transfection studies followed by measu rements of the receptor expression,and receptor mRNA half-life. The results show that the inhibitory effect exerted by the 3.51 kb 3' UTR of the LHR r esides in the distal 1.98 kb region. Half-life measurement of LHR mRNA show ed that the inhibitory effect of the 3' UTR was due to a decrease in recept or mRNA stability, Deletion studies revealed that the entire 1.98 kb region is required for LHR mRNA destabilization. Although the 3.51 Bb 3' UTR of L HR contains 11 AUUUA motifs, their removal had no effect on mRNA stability or receptor expression. Thus, although AUUUA motifs have been implicated in mRNA stability, these motifs do not appear to play an inhibitory role in L HR expression, The 3' UTR of LHR was also able to decrease the expression o f a reporter gene indicating that the inhibitory effect of 3' UTR is not un ique to the open reading frame of LHR, The present studies show that the di stal 1.98 kb portion of the 3' UTR exerts an inhibitory effect on the expre ssion of LHR by decreasing the receptor mRNA half-life. The inhibitory effe ct of 3' UTR might play a role in the maintenance of the steady state level s of the receptor mRNA under different physiological states. (C) 2000 Feder ation of European Biochemical Societies.