A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells

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...

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Bibliographic Details
Published in:Nature communications 2016-07, Vol.7 (1), p.12209-12209, Article 12209
Main Authors: Tichon, Ailone, Gil, Noa, Lubelsky, Yoav, Havkin Solomon, Tal, Lemze, Doron, Itzkovitz, Shalev, Stern-Ginossar, Noam, Ulitsky, Igor
Format: Article
Language:English
Subjects:
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Binding sites
Cell division
Cell Division - genetics
Cell Line, Tumor
Chromosome Segregation - genetics
Cytoplasm
Gene expression
Gene Expression Regulation
Genomes
HeLa Cells
Humanities and Social Sciences
Humans
MicroRNAs
multidisciplinary
Proteins
RNA, Long Noncoding - genetics
RNA, Messenger - metabolism
RNA-Binding Proteins - metabolism
Science
Science (multidisciplinary)
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Summary: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. The human genome contains thousands of long noncoding RNAs which have been preserved by evolution, through their functions are poorly described. Here the authors show that NORAD binds the Pumilo homologues PUM1 and PUM2 to regulate mRNA levels of genes involved in chromosome segregation.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms12209