miR-483 is a self-regulating microRNA and can activate its own expression via USF1 in HeLa cells.
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.
Department of Gene Therapy, Ulm University, Helmholtz Strasse 8/1, 89081 Ulm, Germany. Electronic address: verena.fischer@sartorius-stedim.com.
Verena Vanessa
VV
Emmerling
Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35, 88400 Biberach, Germany. Electronic address: simon.fischer@boehringer-ingelheim.com.
Simon
S
Fischer
Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35, 88400 Biberach, Germany. Electronic address: kleemann@hochschule-bc.de.
Michael
M
Kleemann
Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35, 88400 Biberach, Germany. Electronic address: handrick@hochschule-bc.de.
René
R
Handrick
Department of Gene Therapy, Ulm University, Helmholtz Strasse 8/1, 89081 Ulm, Germany. Electronic address: stefan.kochanek@uni-ulm.de.
Stefan
S
Kochanek
Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35, 88400 Biberach, Germany. Electronic address: otte@hochschule-bc.de.
Kerstin
K
Otte
D006367:HeLa Cells; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D007438:Introns / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D013696:Temperature; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation; D051720:Upstream Stimulatory Factors / Q000235:genetics*
C035170:IGF2 protein, human; C548912:MIRN483 microRNA, human; D035683:MicroRNAs; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; D007335:Insulin-Like Growth Factor II
HeLa; Self-regulation; Transcription factor; miR-483; microRNA