TAILIEUCHUNG - Báo cáo khoa học: Regulation of luteinizing hormone receptor mRNA expression by mevalonate kinase – role of the catalytic center in mRNA recognition

We have shown that hormone-induced downregulation of luteinizing hor-mone receptor (LHR) in the ovary is post-transcriptionally regulated by an mRNA binding protein. This protein, later identified as mevalonate kinase (MVK), binds to the coding region of LHR mRNA, suppresses its transla-tion, and the resulting ribonucleoprotein complex is targeted for degrada-tion. | ỊFEBS Journal Regulation of luteinizing hormone receptor mRNA expression by mevalonate kinase - role of the catalytic center in mRNA recognition Anil K. Nair1 2 Matthew A. Young2 3 and K. M. J. Menon1 2 1 Department of Obstetrics Gynecology University of Michigan MedicalCenter Ann Arbor MI USA 2 Department of BiologicalChemistry University of Michigan MedicalCenter Ann Arbor MI USA 3 Bioinformatics Program University of Michigan MedicalCenter Ann Arbor MI USA Keywords LH receptor mevalonate kinase mRNA stability ovary post-transcriptional regulation Correspondence K. M. J. Menon 6428 MedicalScience 1 1301 E. Catherine Street Ann Arbor MI 48109-0617 USA Fax 1 734 936 8617 Tel 1 734 764 8142 E-mail kmjmenon@ Received 24 January 2008 revised 2 April 2008 accepted 30 April 2008 doi We have shown that hormone-induced downregulation of luteinizing hormone receptor LHR in the ovary is post-transcriptionally regulated by an mRNA binding protein. This protein later identified as mevalonate kinase MVK binds to the coding region of LHR mRNA suppresses its translation and the resulting ribonucleoprotein complex is targeted for degradation. Mutagenesis and crystallographic studies of rat MVK have established Ser146 Glu193 Asp204 and Lys13 as being crucial for its catalytic function. The present study examined the structural aspects of MVK required for LHR mRNA recognition and translational suppression. Single MVK mutants S146A E193Q D204N and K13A were overexpressed in 293T cells. Cytosolic fractions were examined for LHR mRNA binding activities by RNA electrophoretic mobility shift analysis. All the single MVK mutants showed decreased LHR mRNA binding activity compared with the wild-type MVK. Double mutants S146A E193Q E193Q D204N and E193Q K13A of MVK also showed a significant decrease in binding to LHR mRNA suggesting that the residues required for catalytic function are also involved in LHR mRNA recognition. Mutation of the residues

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• intermediate cells
• cell proliferation
• medical analysis
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• medicine
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine