An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2014 Feb 18

PMID 24530304

Citations 229

Authors

Nianwei Lin

Kung-Yen Chang

Zhonghan Li

Keith Gates

Zacharia A Rana

Jason Dang

Danhua Zhang

Tianxu Han

Chao-Shun Yang

Thomas J Cunningham

Steven R Head

Gregg Duester

P Duc Si Dong

Tariq M Rana

Affiliations

Soon will be listed here.

Abstract

Here, we generated a genome-scale shRNA library targeting long intergenic noncoding RNAs (lincRNAs) in the mouse. We performed an unbiased loss-of-function study in mouse embryonic stem cells (mESCs) and identified 20 lincRNAs involved in the maintenance of pluripotency. Among these, TUNA (Tcl1 Upstream Neuron-Associated lincRNA, or megamind) was required for pluripotency and formed a complex with three RNA-binding proteins (RBPs). The TUNA-RBP complex was detected at the promoters of Nanog, Sox2, and Fgf4, and knockdown of TUNA or the individual RBPs inhibited neural differentiation of mESCs. TUNA showed striking evolutionary conservation of both sequence- and CNS-restricted expression in vertebrates. Accordingly, knockdown of tuna in zebrafish caused impaired locomotor function, and TUNA expression in the brains of Huntington's disease patients was significantly associated with disease grade. Our results suggest that the lincRNA TUNA plays a vital role in pluripotency and neural differentiation of ESCs and is associated with neurological function of adult vertebrates.

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