Menon K M J, Nair Anil K, Wang Lei
Department of Obstetrics/Gynecology, University of Michigan Medical Center, Ann Arbor, MI 48109 0617, USA.
Mol Cell Endocrinol. 2006 Feb 26;246(1-2):135-41. doi: 10.1016/j.mce.2005.11.026. Epub 2006 Jan 6.
Luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor, a member of the rhodopsin/beta(2) adrenergic receptor subfamily of G-protein coupled receptors, is expressed primarily in the gonads and essential for the regulation of reproductive function. In the ovary, the expression of the receptor is post-transcriptionally regulated under physiological conditions. Studies from our laboratory showed that the ligand-induced down-regulation of the receptor occurs by accelerated degradation of the mRNA rather than by decreased transcription. We have identified a cytoplasmic LHR mRNA binding protein (LRBP) as a trans-acting factor in regulating LHR mRNA levels. LRBP binds to the coding region of LHR mRNA and causes accelerated degradation of mRNA. The RNA binding activity of LRBP was found to be inversely correlated to LH/hCG receptor mRNA levels. LRBP was purified to homogeneity and its identity was established as mevalonate kinase by N-terminal microsequencing and MALDI analysis. Mevalonate kinase, an enzyme involved in de novo synthesis of cholesterol, belongs to the GHMP family of kinases having a potential RNA binding fold. The expression of MVK mRNA and MVK protein levels were induced in response to hCG treatment prior to the down-regulation of LH/hCG receptor mRNA expression. A model for the post-transcriptional regulation of LH/hCG receptor in the ovary by mevalonate kinase is proposed.
促黄体生成素/人绒毛膜促性腺激素（LH/hCG）受体是G蛋白偶联受体视紫红质/β₂肾上腺素能受体亚家族的成员，主要在性腺中表达，对生殖功能的调节至关重要。在卵巢中，该受体的表达在生理条件下受到转录后调控。我们实验室的研究表明，配体诱导的受体下调是通过mRNA的加速降解而非转录减少发生的。我们已鉴定出一种细胞质LHR mRNA结合蛋白（LRBP）作为调节LHR mRNA水平的反式作用因子。LRBP与LHR mRNA的编码区结合并导致mRNA加速降解。发现LRBP的RNA结合活性与LH/hCG受体mRNA水平呈负相关。LRBP被纯化至同质，并通过N端微量测序和基质辅助激光解吸电离分析确定其为甲羟戊酸激酶。甲羟戊酸激酶是一种参与胆固醇从头合成的酶，属于具有潜在RNA结合结构域的GHMP激酶家族。在LH/hCG受体mRNA表达下调之前，hCG处理可诱导MVK mRNA和MVK蛋白水平的表达。提出了甲羟戊酸激酶对卵巢中LH/hCG受体进行转录后调控的模型。
