A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells.
Ailone TichonNoa GilYoav LubelskyTal Havkin SolomonDoron LemzeShalev ItzkovitzNoam Stern-GinossarIgor UlitskyPublished in: Nature communications (2016)
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.
Keyphrases
- long noncoding rna
- transcription factor
- genome wide identification
- genome wide analysis
- genome wide
- endothelial cells
- single cell
- high frequency
- network analysis
- signaling pathway
- induced pluripotent stem cells
- cell therapy
- copy number
- stem cells
- gene expression
- pluripotent stem cells
- binding protein
- dna methylation
- nucleic acid
- bioinformatics analysis