title: p38 mitogen-activated protein kinase/Hog1p regulates translation of the AU-rich-element-bearing MFA2 transcript.
abstract: AU-rich-element (ARE)-mediated mRNA regulation occurs in Saccharomyces cerevisiae in response to external and internal stimuli through the p38 mitogen-activated protein kinase (MAPK)/Hog1p pathway. We demonstrate that the ARE-bearing MFA2 3' untranslated region (UTR) controls translation efficiency in a p38 MAPK/Hog1p-dependent manner in response to carbon source growth conditions. The carbon source-regulated effect on MFA2 3'-UTR-controlled translation involves the role of conserved ARE binding proteins, the ELAV/TIA-1-like Pub1p, which can interact with the cap/eIF4G complex, and the translation/mRNA stability factor poly(A) binding protein (Pab1p). Pub1p binds the MFA2 3'-UTR in a p38 MAPK/Hog1p-regulated manner in response to carbon source growth conditions. Significantly, the p38 MAPK/Hog1p is also required to modulate Pab1p in response to carbon source. We find that Pab1p can bind the MFA2 3'-UTR in a regulated manner to control MFA2 3'-UTR reporter translation. Binding of full-length Pab1p to the MFA2 3'-UTR correlates with translation repression. Importantly, Pab1p binds the MFA2 3'-UTR only in a PUB1 strain, and correlating with this requirement, Pub1p controls translation repression of MFA2 in a carbon source/Hog1p-regulated manner. These results suggest that the p38 MAPK/Hog1p pathway regulates 3'-UTR-mediated translation by modulating recruitment of Pab1p and Pub1p, which can interact with the translation machinery.
authors.affiliation: Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and Rutgers University, 675 Hoes Lane, Piscataway, NJ 08854, USA.
authors.forename: Shobha
authors.initials: S
authors.lastname: Vasudevan
authors.forename: Nicole
authors.initials: N
authors.lastname: Garneau
authors.forename: Danny
authors.initials: D
authors.lastname: Tu Khounh
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Peltz
mesh_terms: D020413:3' Untranslated Regions; D002244:Carbon / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D005656:Fungal Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D005800:Genes, Fungal; D017930:Genes, Reporter; D005838:Genotype; D005947:Glucose / Q000494:pharmacology; D005990:Glycerol / Q000494:pharmacology; D008074:Lipoproteins / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D008954:Models, Biological; D010675:Pheromones / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D003432:Cross-Linking Reagents; D005656:Fungal Proteins; D008074:Lipoproteins; C095063:MFA2 protein, S cerevisiae; C402629:MFA2 protein, Ustilago hordei; C083327:PUB1 protein, S cerevisiae; D010675:Pheromones; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C450100:pab1 protein, S cerevisiae; D002244:Carbon; D004247:DNA; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D005990:Glycerol