miR-483 is a self-regulating microRNA and can activate its own expression via USF1 in HeLa cells

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• 作者：Verena Vanessa Emmerling^a ; ¹ ; ² ; ^{verena.fischer@sartorius-stedim.com" class="auth_mail" title="E-mail the corresponding author} ; Simon Fischer^b ; ¹ ; ³ ; ^{simon.fischer@boehringer-ingelheim.com" class="auth_mail" title="E-mail the corresponding author} ; Michael Kleemann^b ; ^{kleemann@hochschule-bc.de" class="auth_mail" title="E-mail the corresponding author} ; René ; Handrick^b ; ^{handrick@hochschule-bc.de" class="auth_mail" title="E-mail the corresponding author} ; Stefan Kochanek^a ; ^{stefan.kochanek@uni-ulm.de" class="auth_mail" title="E-mail the corresponding author} ; Kerstin Otte^b ; ^{otte@hochschule-bc.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：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
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：80
• 期：Complete
• 页码：81-86
• 全文大小：1190 K

文摘

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.