MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2.
MicroRNAs are small, non-coding RNAs that posttranscriptionally regulate gene expression mainly by binding to the 3'UTR of their target mRNAs. Recent data revealed that microRNAs have an important role in pancreas and liver development and physiology. Using cloning and microarray profiling approaches, we show that a unique repertoire of microRNAs is expressed at the onset of liver and pancreas organogenesis, and in pancreas and liver at key stages of cell fate determination. Among the microRNAs that are expressed at these stages, miR-495 and miR-218 were predicted to, respectively, target the Onecut (OC) transcription factors Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) and OC-2, two important regulators of liver and pancreas development. MiR-495 and miR-218 are dynamically expressed in developing liver and pancreas, and by transient transfection, we show that they target HNF-6 and OC-2 3'UTRs. Moreover, when overexpressed in cultured cells, miR-495 and miR-218 decrease the endogenous levels of HNF-6 and OC-2 mRNA. These results indicate that the expression of regulators of liver and pancreas development is modulated by microRNAs. They also suggest a developmental role for miR-495 and miR-218.
Simion
Alexandru
A
Université catholique de Louvain, de Duve Institute, 75 Avenue Hippocrate 7529, B-1200 Brussels, Belgium.
Laudadio
Ilaria
I
Prévot
Pierre-Paul
PP
Raynaud
Peggy
P
Lemaigre
Frédéric P
FP
Jacquemin
Patrick
P
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051559:Hepatocyte Nuclear Factor 6 / Q000235:genetics*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D051558:Onecut Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D010179:Pancreas / Q000196:embryology* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D051559:Hepatocyte Nuclear Factor 6; D018398:Homeodomain Proteins; C547684:MIRN218 microRNA, mouse; C547683:MIRN495 microRNA, mouse; D035683:MicroRNAs; C487964:ONECUT2 protein, mouse; D051558:Onecut Transcription Factors; C496606:Onecut1 protein, mouse; D014157:Transcription Factors