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

• DOI: 10.1038/s41467-018-08153-2
• Publication Date: 2019-01-14T10:49:37Z
• Authors: Valentina Profumo; Barbara Forte; Stefano Percio; Federica Rotundo; Valentina Doldi; Elena Ferrari; Nicola Fenderico; Matteo Dugo; Dario Romagnoli; Matteo Benelli; Riccardo Valdagni; Diletta Dolfini; Nadia Zaffaroni; Paolo Gandellini
• Keywords: Male; Ribonuclease III; 570; Science; General Biochemistry,Genetics and Molecular Biology; 610; General Physics and Astronomy; Article; 03 medical and health sciences; Cell Line, Tumor; name=General Biochemistry,Genetics and Molecular Biology; Humans; Promoter Regions, Genetic; Cells, Cultured; Gene Editing; 0303 health sciences; Prostate cancer; /dk/atira/pure/subjectarea/asjc/1300/1300; Q; Prostate; Cell Differentiation; Epithelial Cells; General Chemistry; MicroRNAs; name=General Physics and Astronomy; miRNAs; Long non-coding RNAs; RNA, Long Noncoding; /dk/atira/pure/subjectarea/asjc/3100/3100; CRISPR-Cas Systems; Transcriptome; name=General Chemistry; /dk/atira/pure/subjectarea/asjc/1600/1600

AbstractThough 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).