MiR-483 is a self-regulating microRNA and can activate its own expression via USF1 in HeLa cells. (November 2016)

• Record Type: Journal Article
• Authors: Emmerling, Verena Vanessa; Fischer, Simon; Kleemann, Michael; Handrick, René; Kochanek, Stefan; Otte, Kerstin
• Is Part Of: International journal of biochemistry & cell biology. Volume 80(2016:Nov.)
• Page Start: 81
• Page End: 86
• Publication Date: 2016-11
• Subjects: AGO Argonaute -- bp base pair -- CHO Chinese hamster ovary -- cm2 square centimeter -- CTCF CCCTC-binding factor -- h hour -- IGF2 insulin-like growth factor 2 -- miR microRNA -- miRNA microRNA -- mRNA messenger RNA -- NT non-targeting -- rAAV recombinant adeno-associated virus -- USF1 upstream stimulating factor 1 -- UTR untranslated region; microRNA -- miR-483 -- Self-regulation -- HeLa -- Transcription factor; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2016.09.022
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that constitute a fundamental part of post-transcriptional gene regulation in mammalian cells. We have recently identified the intronic miR-483, which functions as an important regulator of protein synthesis during mild hypothermia in human and rodent cells. Since only very little is known about transcriptional regulation of intronic miRNAs and their host genes, we thoroughly investigated the regulation of miR-483 expression and its host gene IGF2 in HeLa cells. We demonstrate that miR-483 is regulated and expressed independently of its host gene IGF2 during mild hypothermia. Strikingly, we also discovered that miR-483 enhances its own transcription by up-regulation of the transcription factor USF1, which activates a promoter element upstream of the MIR483 gene. However, since the USF1 mRNA lacks binding sites for miR-483-5p and -3p, USF1 expression is likely enhanced in an indirect manner. Our results suggest that miR-483 may self-regulate its own expression independently of its host gene IGF2 in human HeLa cells. This points towards a novel feed-forward mechanism, in which selected intronic miRNAs may activate their own expression by transcriptional activation of upstream regulators.