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

被引:172
作者
Tichon, Ailone [1 ]
Gil, Noa [1 ]
Lubelsky, Yoav [1 ]
Solomon, Tal Havkin [2 ]
Lemze, Doron [3 ]
Itzkovitz, Shalev [3 ]
Stern-Ginossar, Noam [2 ]
Ulitsky, Igor [1 ]
机构
[1] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel
[2] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel
[3] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
基金
欧洲研究理事会;
关键词
EMBRYONIC STEM-CELLS; MAMMALIAN MICRORNAS; BINDING-PROTEIN; MESSENGER-RNAS; CIRCULAR RNAS; PUF FAMILY; PAR-CLIP; TRANSLATION; IDENTIFICATION; EVOLUTION;
D O I
10.1038/ncomms12209
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:10
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