title: A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells.
abstract: Thousands of long noncoding RNA (lncRNA) genes are encoded in the human genome, and hundreds of them are evolutionarily conserved, but their functions and modes of action remain largely obscure. Particularly enigmatic lncRNAs are those that are exported to the cytoplasm, including NORAD-an abundant and highly conserved cytoplasmic lncRNA. Here we show that most of the sequence of NORAD is comprised of repetitive units that together contain at least 17 functional binding sites for the two mammalian Pumilio homologues. Through binding to PUM1 and PUM2, NORAD modulates the mRNA levels of their targets, which are enriched for genes involved in chromosome segregation during cell division. Our results suggest that some cytoplasmic lncRNAs function by modulating the activities of RNA-binding proteins, an activity which positions them at key junctions of cellular signalling pathways.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ailone
authors.initials: A
authors.lastname: Tichon
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Gil
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Lubelsky
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Havkin Solomon
authors.affiliation: Department of Molecular Cell Biology,Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Lemze
authors.affiliation: Department of Molecular Cell Biology,Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Shalev
authors.initials: S
authors.lastname: Itzkovitz
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Stern-Ginossar
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Igor
authors.identifier: 0000-0003-0555-6561
authors.initials: I
authors.lastname: Ulitsky
mesh_terms: D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D020090:Chromosome Segregation / Q000235:genetics*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: C000607950:NORAD long non-coding RNA, human; C471242:PUM1 protein, human; C471243:PUM2 protein, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D016601:RNA-Binding Proteins