title: Polyribosome and ribonucleoprotein complex redistribution of mRNA induced by GnRH involves both EIF2AK3 and MAPK signaling.
abstract: The neuropeptide gonadotropin-releasing hormone stimulates synthesis and secretion of the glycoprotein gonadotropic hormones and activates the unfolded protein response, which causes a transient reduction of endoplasmic reticulum-associated mRNA translation. Hormone-treated cell extracts were fractionated to resolve mRNA in active polyribosomes from mRNA in inactive complexes. Quantitative real-time PCR and expression array analysis were used to determine hormone-induced redistribution of mRNAs between fractions and individual mRNAs were found to be redistributed differentially. Among the affected mRNAs relevant to gonadotropin synthesis, the luteinizing hormone subunit genes Lhb and Cga were enriched in the ribonucleoprotein pool. The MAP kinase phosphatase Dusp1 was enriched in the polyribosome pool. Enrichment of Dusp1 mRNA in the polyribosome pool was independent of the unfolded protein response, sensitive to ERK inhibition, and dependent on the 3'untranslated region. The results show that GnRH exerts translational control to modulate physiologically relevant gene expression through two distinct signaling pathways.
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: Minh-Ha T
authors.initials: MT
authors.lastname: Do
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: Taeshin
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: Hiral
authors.initials: H
authors.lastname: Dave
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Intriago
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: Uriah A
authors.initials: UA
authors.lastname: Astorga
authors.affiliation: Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA 92093, United States. Electronic address: mlawson@ucsd.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lawson
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002460:Cell Line; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D051959:ELAV Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D011132:Polyribosomes / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D056811:Unfolded Protein Response / Q000187:drug effects; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D054638:Dual Specificity Phosphatase 1; D051959:ELAV Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D007987:Gonadotropin-Releasing Hormone; D011493:Protein Kinase C; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D020123:Sirolimus; D013755:Tetradecanoylphorbol Acetate; D019892:eIF-2 Kinase; C517020:Dusp1 protein, mouse
keywords: Dusp1; Gonadotropins; Luteinizing hormone; Pituitary; Translation; Unfolded protein response