title: RNA-binding protein HuR sequesters microRNA-21 to prevent translation repression of proinflammatory tumor suppressor gene programmed cell death 4.
abstract: Translation control of proinflammatory genes has a crucial role in regulating the inflammatory response and preventing chronic inflammation, including a transition to cancer. The proinflammatory tumor suppressor protein programmed cell death 4 (PDCD4) is important for maintaining the balance between inflammation and tumorigenesis. PDCD4 messenger RNA translation is inhibited by the oncogenic microRNA, miR-21. AU-rich element-binding protein HuR was found to interact with the PDCD4 3'-untranslated region (UTR) and prevent miR-21-mediated repression of PDCD4 translation. Cells stably expressing miR-21 showed higher proliferation and reduced apoptosis, which was reversed by HuR expression. Inflammatory stimulus caused nuclear-cytoplasmic relocalization of HuR, reversing the translation repression of PDCD4. Unprecedentedly, HuR was also found to bind to miR-21 directly, preventing its interaction with the PDCD4 3'-UTR, thereby preventing the translation repression of PDCD4. This suggests that HuR might act as a 'miRNA sponge' to regulate miRNA-mediated translation regulation under conditions of stress-induced nuclear-cytoplasmic translocation of HuR, which would allow fine-tuned gene expression in complex regulatory environments.
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research, Kolkata, India.
authors.forename: D K
authors.initials: DK
authors.lastname: Poria
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research, Kolkata, India.
authors.forename: A
authors.initials: A
authors.lastname: Guha
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research, Kolkata, India.
authors.forename: I
authors.initials: I
authors.lastname: Nandi
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research, Kolkata, India.
authors.forename: P S
authors.initials: PS
authors.lastname: Ray
mesh_terms: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D018836:Inflammation Mediators; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins