title: Relief of microRNA-mediated translational repression in human cells subjected to stress.
abstract: In metazoans, most microRNAs imperfectly base-pair with the 3' untranslated region (3'UTR) of target mRNAs and prevent protein accumulation by either repressing translation or inducing mRNA degradation. Examples of specific mRNAs undergoing microRNA-mediated repression are numerous, but whether the repression is a reversible process remains largely unknown. Here we show that cationic amino acid transporter 1 (CAT-1) mRNA and reporters bearing its 3'UTR can be relieved from the microRNA miR-122-induced inhibition in human hepatocarcinoma cells subjected to different stress conditions. The derepression of CAT-1 mRNA is accompanied by its release from cytoplasmic processing bodies and its recruitment to polysomes. The derepression requires binding of HuR, an AU-rich-element binding protein, to the 3'UTR of CAT-1 mRNA. We propose that proteins interacting with the 3'UTR will generally act as modifiers altering the potential of miRNAs to repress gene expression.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, P.O. Box 2543, 4002 Basel, Switzerland.
authors.forename: Suvendra N
authors.initials: SN
authors.lastname: Bhattacharyya
authors.forename: Regula
authors.initials: R
authors.lastname: Habermacher
authors.forename: Ursula
authors.initials: U
authors.lastname: Martine
authors.forename: Ellen I
authors.initials: EI
authors.lastname: Closs
authors.forename: Witold
authors.initials: W
authors.lastname: Filipowicz
mesh_terms: D020413:3' Untranslated Regions; D000596:Amino Acids / Q000172:deficiency; D000954:Antigens, Surface / Q000378:metabolism; D018053:Arsenites / Q000494:pharmacology; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003470:Culture Media; D022083:Cytoplasmic Structures / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D018384:Oxidative Stress; D011485:Protein Binding; D014176:Protein Biosynthesis; D020871:RNA Stability; D034443:RNA Transport; D016601:RNA-Binding Proteins / Q000378:metabolism; D017670:Sodium Compounds / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D000596:Amino Acids; D000954:Antigens, Surface; D018053:Arsenites; D027201:Cationic Amino Acid Transporter 1; D003470:Culture Media; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C420825:SLC7A1 protein, human; D017670:Sodium Compounds; C017947:sodium arsenite; D019284:Thapsigargin