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

Ailone Tichon; Noa Gil; Yoav Lubelsky; Tal Havkin Solomon; Doron Lemze; Shalev Itzkovitz; Noam Stern-Ginossar; Igor Ulitsky

doi:10.1038/ncomms12209

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

Ailone Tichon
, Noa Gil
, Yoav Lubelsky
, Tal Havkin Solomon
, Doron Lemze
, Shalev Itzkovitz
, Noam Stern-Ginossar
, Igor Ulitsky

Research output: Contribution to journal › Article › peer-review

183 Scopus citations

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.

Original language	English
Article number	12209
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12209
State	Published - 13 Jul 2016
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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10.1038/ncomms12209

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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.",

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T1 - A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells

AU - Tichon, Ailone

AU - Gil, Noa

AU - Lubelsky, Yoav

AU - Solomon, Tal Havkin

AU - Lemze, Doron

AU - Itzkovitz, Shalev

AU - Stern-Ginossar, Noam

AU - Ulitsky, Igor

PY - 2016/7/13

Y1 - 2016/7/13

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms12209

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JO - Nature Communications

JF - Nature Communications

M1 - 12209

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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