TY - JOUR
T1 - LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation
AU - Profumo, Valentina
AU - Forte, Barbara
AU - Percio, Stefano
AU - Rotundo, Federica
AU - Doldi, Valentina
AU - Ferrari, Elena
AU - Fenderico, Nicola
AU - Dugo, Matteo
AU - Romagnoli, Dario
AU - Benelli, Matteo
AU - Valdagni, Riccardo
AU - Dolfini, Diletta
AU - Zaffaroni, Nadia
AU - Gandellini, Paolo
N1 - Funding Information:
We thank R. El Bezawy, G. Cimino-Reale, and M. Colecchia for helpful technical assistance, and F. Nicassio, M. Folini, and R. Mantovani for constructive discussions. We thank the Platform of Integrated Biology of Fondazione IRCCS Istituto Nazionale dei Tumori for microarray experiments. We are also grateful to D. Majerna for help in language editing. This work was supported by grants from: Italian Ministry of Health (GR-2013-02355625 to P.G.), CARIPLO Foundation (2015-0866 to P.G.), and I. Mon-zino Foundation (to N.Z.).
Copyright:
© 2019, The Author(s).
PY - 2019/1/18
Y1 - 2019/1/18
N2 - Though miR-205 function has been largely characterized, the nature of its host gene, MIR205HG, is still completely unknown. Here, we show that only lowly expressed alternatively spliced MIR205HG transcripts act as de facto pri-miRNAs, through a process that involves Drosha to prevent unfavorable splicing and directly mediate miR-205 excision. Notably, MIR205HG-specific processed transcripts revealed to be functional per se as nuclear long noncoding RNA capable of regulating differentiation of human prostate basal cells through control of the interferon pathway. At molecular level, MIR205HG directly binds the promoters of its target genes, which have an Alu element in proximity of the Interferon-Regulatory Factor (IRF) binding site, and represses their transcription likely buffering IRF1 activity, with the ultimate effect of preventing luminal differentiation. As MIR205HG functions autonomously from (albeit complementing) miR-205 in preserving the basal identity of prostate epithelial cells, it warrants reannotation as LEADeR (Long Epithelial Alu-interacting Differentiation-related RNA).
AB - Though miR-205 function has been largely characterized, the nature of its host gene, MIR205HG, is still completely unknown. Here, we show that only lowly expressed alternatively spliced MIR205HG transcripts act as de facto pri-miRNAs, through a process that involves Drosha to prevent unfavorable splicing and directly mediate miR-205 excision. Notably, MIR205HG-specific processed transcripts revealed to be functional per se as nuclear long noncoding RNA capable of regulating differentiation of human prostate basal cells through control of the interferon pathway. At molecular level, MIR205HG directly binds the promoters of its target genes, which have an Alu element in proximity of the Interferon-Regulatory Factor (IRF) binding site, and represses their transcription likely buffering IRF1 activity, with the ultimate effect of preventing luminal differentiation. As MIR205HG functions autonomously from (albeit complementing) miR-205 in preserving the basal identity of prostate epithelial cells, it warrants reannotation as LEADeR (Long Epithelial Alu-interacting Differentiation-related RNA).
KW - Long non-coding RNAs
KW - miRNAs
KW - Prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=85060175446&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-08153-2
DO - 10.1038/s41467-018-08153-2
M3 - Article
C2 - 30659180
AN - SCOPUS:85060175446
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
M1 - 307
ER -