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Mol Cell. 2014 Mar 20;53(6):1005-19. doi: 10.1016/j.molcel.2014.01.021. Epub 2014 Feb 13.

An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment.

Author information

1
Program for RNA Biology, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
2
Program for Genetic Disease, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
3
Program for Development and Aging, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
4
The Scripps Research Institute, Microarray and NGS Core Facility, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
5
Program for RNA Biology, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Pediatrics, Rady Children's Hospital San Diego and University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: trana@sanfordburnham.org.

Erratum in

  • Mol Cell. 2014 Mar 20;53(6):1067.

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.

PMID:
24530304
PMCID:
PMC4010157
DOI:
10.1016/j.molcel.2014.01.021
[Indexed for MEDLINE]
Free PMC Article

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