microRNA-17-92 cluster is a direct Nanog target and controls neural stem cell through Trp53inp1.
The transcription factor Nanog plays a critical role in the self-renewal of embryonic stem cells as well as in neural stem cells (NSCs). microRNAs (miRNAs) are also involved in stemness regulation. However, the miRNA network downstream of Nanog is still poorly understood. High-throughput screening of miRNA expression profiles in response to modulated levels of Nanog in postnatal NSCs identifies miR-17-92 cluster as a direct target of Nanog. Nanog controls miR-17-92 cluster by binding to the upstream regulatory region and maintaining high levels of transcription in NSCs, whereas Nanog/promoter association and cluster miRNAs expression are lost alongside differentiation. The two miR-17 family members of miR-17-92 cluster, namely miR-17 and miR-20a, target Trp53inp1, a downstream component of p53 pathway. To support a functional role, the presence of miR-17/20a or the loss of Trp53inp1 is required for the Nanog-induced enhancement of self-renewal of NSCs. We unveil an arm of the Nanog/p53 pathway, which regulates stemness in postnatal NSCs, wherein Nanog counteracts p53 signals through miR-17/20a-mediated repression of Trp53inp1.
Department of Molecular Medicine, University of Rome 'La Sapienza', Rome, Italy.
Neha
N
Garg
Agnese
A
Po
Evelina
E
Miele
Antonio Francesco
AF
Campese
Federica
F
Begalli
Marianna
M
Silvano
Paola
P
Infante
Carlo
C
Capalbo
Enrico
E
De Smaele
Gianluca
G
Canettieri
Lucia
L
Di Marcotullio
Isabella
I
Screpanti
Elisabetta
E
Ferretti
Alberto
A
Gulino
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D018398:Homeodomain Proteins; C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; C498965:Trp53inp1 protein, mouse