LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.

Abstract:

: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).

journal_name

Nat Commun

journal_title

Nature communications

authors

Profumo V,Forte B,Percio S,Rotundo F,Doldi V,Ferrari E,Fenderico N,Dugo M,Romagnoli D,Benelli M,Valdagni R,Dolfini D,Zaffaroni N,Gandellini P

doi

10.1038/s41467-018-08153-2

subject

Has Abstract

pub_date

2019-01-18 00:00:00

pages

307

issue

1

issn

2041-1723

pii

10.1038/s41467-018-08153-2

journal_volume

10

pub_type

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