title: Association of luteinizing hormone receptor (LHR) mRNA with its binding protein leads to decapping and degradation of the mRNA in the p bodies.
abstract: Luteinizing hormone receptor undergoes downregulation during preovulatory Luteinizing hormone surge through a post-transcriptional mechanism involving an RNA binding protein designated as LRBP. The present study examined the mechanism by which LRBP induces the degradation of Luteinizing hormone receptor mRNA, specifically the role of decapping of Luteinizing hormone receptor mRNA and the translocation of LRBP-bound Luteinizing hormone receptor mRNA to degradative machinery. Immunoprecipitation of the complex with the 5'cap structure antibody followed by real time PCR analysis showed progressive loss of capped Luteinizing hormone receptor mRNA during downregulation suggesting that Luteinizing hormone receptor mRNA undergoes decapping prior to degradation. RNA immunoprecipitation analysis confirmed dissociation of eukaryotic initiation factor 4E from the cap structure, a step required for decapping. Furthermore, RNA immunoprecipitation analysis using antibody against the p body marker protein, DCP1A showed that Luteinizing hormone receptor mRNA was associated with the p bodies, the cytoplasmic foci that contain RNA degradative enzymes and decapping complex. Immunohistochemical studies using antibodies against LRBP and DCP1A followed by confocal analysis showed colocalization of LRBP with DCP1A during downregulation. This was further confirmed by co-immunoprecipitation of LRBP with DCP1A. The association of LRBP and Luteinizing hormone receptor mRNA in the p bodies during downregulation was further confirmed by examining the association of a second p body component, rck/p54, using immunoprecipitation and RNA immunoprecipitation respectively. These data suggest that the association of LRBP with Luteinizing hormone receptor mRNA results in the translocation of the messenger ribonucleoprotein complex to the p bodies leading to decapping and degradation.
authors: Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, MI 48109-0617, USA.
authors: Bindu
authors: B
authors: Menon
authors: Jennifer
authors: J
authors: Sinden
authors: K M J
authors: KM
authors: Menon
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor); D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011974:Receptors, LH / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011974:Receptors, LH; D007986:Luteinizing Hormone; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase
references: BMC Genomics. 2005 May 20;6:75
references: 15907206
references: Mol Cell Endocrinol. 2006 Feb 26;246(1-2):135-41
references: 16406262
references: Endocrinology. 1991 Jan;128(1):388-93
references: 1986931
references: Mol Cell. 2007 Mar 9;25(5):635-46
references: 17349952
references: Mol Endocrinol. 2011 Feb;25(2):282-90
references: 21147848
references: J Biol Chem. 2007 Dec 28;282(52):37389-401
references: 17942399
references: RNA. 2002 Dec;8(12):1489-501
references: 12515382
references: Biochim Biophys Acta. 2010 May;1803(5):591-7
references: 20167237
references: EMBO J. 2002 Dec 16;21(24):6915-24
references: 12486012
references: J Cell Biol. 1997 Feb 24;136(4):761-73
references: 9049243
references: RNA Biol. 2007 Jan-Mar;4(1):16-25
references: 17617744
references: Endocrinology. 1990 Jun;126(6):3277-9
references: 2351119
references: Mol Endocrinol. 2007 Sep;21(9):2233-41
references: 17550979
references: Mol Cell Endocrinol. 2005 Apr 15;233(1-2):65-72
references: 15767047
references: Nat Rev Mol Cell Biol. 2007 Feb;8(2):113-26
references: 17245413
references: J Biol Chem. 2004 Apr 9;279(15):14937-44
references: 14749336
references: Biochemistry. 1999 Dec 21;38(51):16889-97
references: 10606523
references: J Biol Chem. 1998 Apr 24;273(17):10658-64
references: 9553128
references: Genes Dev. 2007 Mar 15;21(6):627-31
references: 17369394
references: Mol Cell Endocrinol. 2007 Jan 2;260-262:109-16
references: 17055149
references: Biochem Soc Trans. 2010 Feb;38(Pt 1):242-51
references: 20074068
references: Nucleic Acids Res. 2006 Jun 12;34(10):3082-94
references: 16769775
references: Science. 2003 May 2;300(5620):805-8
references: 12730603
references: Biochim Biophys Acta. 2009 Nov;1793(11):1787-94
references: 19716387
references: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10611-6
references: 12149460
references: J Biol Chem. 2005 Dec 30;280(52):42809-16
references: 16263716
references: Genes Dev. 2005 Feb 1;19(3):351-61
references: 15687258
references: Annu Rev Biochem. 2004;73:861-90
references: 15189161
references: Biochemistry. 1996 Sep 24;35(38):12347-53
references: 8823169
references: J Biol Chem. 2002 Jun 14;277(24):21468-73
references: 11940568
references: Mol Cell. 2008 Dec 5;32(5):605-15
references: 19061636
references: Mol Cell Biol. 2000 Nov;20(21):7933-42
references: 11027264
references: J Cell Biol. 2005 Jun 20;169(6):871-84
references: 15967811
references: Endocrinology. 2008 Apr;149(4):1524-33
references: 18174289
references: Nat Rev Mol Cell Biol. 2007 Jan;8(1):9-22
references: 17183357
references: Mol Endocrinol. 1990 Dec;4(12):1856-65
references: 2127956