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Nat Genet. 2016 Jan;48(1):44-52. doi: 10.1038/ng.3449. Epub 2015 Nov 23.

The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear reprogramming.

Author information

1
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.
2
Department of Genetics, Stanford University, Stanford, California, USA.
3
Department of Obstetrics and Gynecology, Stanford University, Stanford, California, USA.
4
Department of Pathology, Stanford University, Stanford, California, USA.
5
Department of Statistics, Stanford University, Stanford, California, USA.
6
Department of Chemical and Systems Biology, Stanford University, Stanford, California, USA.
7
Department of Developmental Biology, Stanford University, Stanford, California, USA.

Abstract

Long intergenic noncoding RNAs (lincRNAs) are derived from thousands of loci in mammalian genomes and are frequently enriched in transposable elements (TEs). Although families of TE-derived lincRNAs have recently been implicated in the regulation of pluripotency, little is known of the specific functions of individual family members. Here we characterize three new individual TE-derived human lincRNAs, human pluripotency-associated transcripts 2, 3 and 5 (HPAT2, HPAT3 and HPAT5). Loss-of-function experiments indicate that HPAT2, HPAT3 and HPAT5 function in preimplantation embryo development to modulate the acquisition of pluripotency and the formation of the inner cell mass. CRISPR-mediated disruption of the genes for these lincRNAs in pluripotent stem cells, followed by whole-transcriptome analysis, identifies HPAT5 as a key component of the pluripotency network. Protein binding and reporter-based assays further demonstrate that HPAT5 interacts with the let-7 microRNA family. Our results indicate that unique individual members of large primate-specific lincRNA families modulate gene expression during development and differentiation to reinforce cell fate.

PMID:
26595768
PMCID:
PMC4827613
DOI:
10.1038/ng.3449
[Indexed for MEDLINE]
Free PMC Article

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