Post-transcriptional Regulation of Luteinizing Hormone Receptor mRNA Expression in the Ovary

Abstract

Regulated degradation of luteinizing hormone receptor (LHR) mRNA through post-transcriptional mechanisms plays an important role in regulating LH receptor expression in response to changes in the secretion of LH from the pituitary gland. A specific LHR mRNA binding protein (LRBP), identified as mevalonate kinase, binds to nucleotides 203–220 in the coding region of LHR mRNA and exhibits specificity for this region. The LHR mRNA binding protein caused accelerated LHR mRNA decay through translational suppression of LHR mRNA. Furthermore, LRBP interacts with other proteins identified by yeast two hybrid screens. Among these, eukaryotic initiation factor 5A (eIF5A) undergoes hypusination and plays a regulatory role by interacting with LHR mRNA-LRBP complex. Inhibition of hypusination of eIF5A reduces the ability of LHR mRNA to undergo ligand-induced downregulation. We have identified a small non-coding RNA, miR-122 that plays a role in LHR mRNA expression by regulating LRBP via sterol regulatory element binding protein (SREBP). The post-transcriptional mechanism described here provides a novel means to regulate the steady state levels of LHR, a molecule that plays a central role in mammalian reproduction, by controlling the degradation of its mRNA during ovarian cycle.