Premium
Post‐transcriptional Regulation of Luteinizing Hormone Receptor Expression by Mevalonate Kinase, a novel mRNA binding Protein
Author(s) -
Nair Anil K,
Me K.M.J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.994.3
Subject(s) - biology , messenger rna , microbiology and biotechnology , binding site , gene expression , biochemistry , gene
There is increasing evidence that metabolic enzymes act as RNA binding proteins and regulate gene expression post‐transcriptionally. We have identified mevalonate kinase (MVK), an enzyme involved in cholesterol biosynthesis, as a trans ‐factor for luteinizing hormone receptor (LHR) mRNA. LHR is one of the crucial G protein‐coupled receptors that plays a key role in mammalian reproduction. MVK binds to the coding region of LHR mRNA and accelerates its degradation in vitro . Translation studies have shown that MVK inhibits translation of LHR mRNA. Endogenous association of LHR mRNA with MVK has also been detected by immunoprecipitation of the ribonucleoprotein complex with MVK antibody. Studies were then performed to examine the structural aspects of MVK required for LHR mRNA recognition. A concentration dependent decrease in LHR mRNA binding activity of MVK by its substrates, ATP and mevalonate, indirectly indicated the involvement of the active site for RNA binding. The role of the active site of MVK for LHR mRNA binding was tested using mutations of the amino acids required for catalysis. The results showed that mutations of Ser 146 , Glu 193 , Asp 204 and Lys 13 reduce LHR mRNA binding activity of MVK. To examine the biological effects of these mutants on LHR mRNA expression, rat LHR mRNA was translated in the presence of the MVK mutant proteins. The results showed that mutations of the active site residues abrogated the inhibitory effect on LHR mRNA translation. From these results we conclude that the intact active site of MVK is required for its binding to LHR mRNA and for its translational suppressor function. (Supported by NIH Grant R37 HD 06656)