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

Posttranscriptional regulation of luteinizing hormone receptor (LHR) mRNA has a significant role in regulating cell surface receptor expression during ovarian cycle. In order to gain insight into the mechanism of posttranscriptional regulation, the cis-acting elements in the 3' untranslated region (3' UTR) of LHR mRNA were examined by transfection studies followed by measurements 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 resides in the distal 1.98 kb region. Half-life measurement of LHR mRNA showed that the inhibitory effect of the 3' UTR was due to a decrease in receptor mRNA stability. Deletion studies revealed that the entire 1.98 kb region is required for LHR mRNA destabilization. Although the 3.51 kb 3' UTR of LHR 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 LHR expression. The 3' UTR of LHR was also able to decrease the expression of a reporter gene indicating that the inhibitory effect of 3' UTR is not unique to the open reading frame of LHR. The present studies show that the distal 1.98 kb portion of the 3' UTR exerts an inhibitory effect on the expression of LHR by decreasing the receptor mRNA half-life. The inhibitory effect of 3' UTR might play a role in the maintenance of the steady state levels of the receptor mRNA under different physiological states.