title: Regulation of pri-miRNA processing by a long noncoding RNA transcribed from an ultraconserved region.
abstract: Noncoding RNAs (ncRNAs) control cellular programs by affecting protein-coding genes, but evidence increasingly points to their involvement in a network of ncRNA-ncRNA interactions. Here, we show that a long ncRNA, Uc.283+A, controls pri-miRNA processing. Regulation requires complementarity between the lower stem region of the pri-miR-195 transcript and an ultraconserved sequence in Uc.283+A, which prevents pri-miRNA cleavage by Drosha. Mutation of the site in either RNA molecule uncouples regulation in vivo and in vitro. We propose a model in which lower-stem strand invasion by Uc.283+A impairs microprocessor recognition and efficient pri-miRNA cropping. In addition to identifying a case of RNA-directed regulation of miRNA biogenesis, our study reveals regulatory networks involving different ncRNA classes of importance in cancer.
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, 08908 Barcelona, Catalonia, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Liz
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, 08908 Barcelona, Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Portela
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, 08908 Barcelona, Catalonia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Soler
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, 08908 Barcelona, Catalonia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez
authors.affiliation: Experimental Therapeutics & Cancer Genetics, MD Anderson Cancer Center, Texas State University, Houston, TX 77030, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Ling
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Edinburgh, EH9 3JR, UK.
authors.forename: Gracjan
authors.initials: G
authors.lastname: Michlewski
authors.affiliation: Experimental Therapeutics & Cancer Genetics, MD Anderson Cancer Center, Texas State University, Houston, TX 77030, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, 08908 Barcelona, Catalonia, Spain. Electronic address: sguil@idibell.cat.
authors.forename: Sònia
authors.initials: S
authors.lastname: Guil
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, 08908 Barcelona, Catalonia, Spain; School of Medicine, Department of Physiological Sciences II, University of Barcelona, 08036 Barcelona, Catalonia, Spain; Institucio Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Catalonia, Spain. Electronic address: mesteller@idibell.cat.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D017124:Conserved Sequence; D045325:HCT116 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D062085:RNA, Long Noncoding / Q000378:metabolism / Q000502:physiology*
chemical_list: C552722:MIRN195 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding