title: Regulation of cyclin-dependent kinase 4 translation through CUG-binding protein 1 and microRNA-222 by polyamines.
abstract: The amino acid-derived polyamines are organic cations that are essential for growth in all mammalian cells, but their exact roles at the molecular level remain largely unknown. Here we provide evidence that polyamines promote the translation of cyclin-dependent kinase 4 (CDK4) by the action of CUG-binding protein 1 (CUGBP1) and microRNA-222 (miR-222) in intestinal epithelial cells. Both CUGBP1 and miR-222 were found to bind the CDK4 mRNA coding region and 3'-untranslated region and repressed CDK4 translation synergistically. Depletion of cellular polyamines increased cytoplasmic CUGBP1 abundance and miR-222 levels, induced their associations with the CDK4 mRNA, and inhibited CDK4 translation, whereas increasing the levels of cellular polyamines decreased CDK4 mRNA interaction with CUGBP1 and miR-222, in turn inducing CDK4 expression. Polyamine-deficient cells exhibited an increased colocalization of tagged CDK4 mRNA with processing bodies; this colocalization was abolished by silencing CUGBP1 and miR-222. Together, our findings indicate that polyamine-regulated CUGBP1 and miR-222 modulate CDK4 translation at least in part by altering the recruitment of CDK4 mRNA to processing bodies.
authors: Cell Biology Group, Department of Surgery University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Lan
authors: L
authors: Xiao
authors: Yu-Hong
authors: YH
authors: Cui
authors: Jaladanki N
authors: JN
authors: Rao
authors: Tongtong
authors: T
authors: Zou
authors: Lan
authors: L
authors: Liu
authors: Alexis
authors: A
authors: Smith
authors: Douglas J
authors: DJ
authors: Turner
authors: Myriam
authors: M
authors: Gorospe
authors: Jian-Ying
authors: JY
authors: Wang
mesh_terms: D000818:Animals; D000067879:CELF1 Protein; D049109:Cell Proliferation; D002478:Cells, Cultured; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis*; D000518:Eflornithine / Q000494:pharmacology; D057075:Enzyme Assays; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D020868:Gene Silencing; D017930:Genes, Reporter; D007413:Intestinal Mucosa / Q000166:cytology; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000378:metabolism*; D016366:Open Reading Frames; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D065108:Ornithine Decarboxylase Inhibitors; D011485:Protein Binding; D014176:Protein Biosynthesis; D011700:Putrescine / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D013095:Spermidine / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000067879:CELF1 Protein; C000594460:Celf1 protein, rat; C568897:MIRN222 microRNA, rat; D035683:MicroRNAs; D065108:Ornithine Decarboxylase Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D013096:Spermine; D049409:Luciferases, Firefly; D051358:Cyclin-Dependent Kinase 4; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine