The Primate-Specific Noncoding RNA HPAT5 Regulates Pluripotency During Human Preimplantation Development and Nuclear Reprogramming  

Oleh:

Durruthy, Jens ; Sebastiano, Vittorio ; Wossidlo, Mark ; Cepeda, Diana ; Jun Cui ; Grow, Edward J. ; Davila, Jonathan ; Mall, Moritz ; Wing H. Wong ; Wysocka, Joanna ; Kin Fai Au ; Pera, Renee A. Reijo

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 48 no. 01 (Jan. 2016), page 44-52.
Topik: Cell Biology; Cell Lineage; Gene Regulation; Stem Cells

Ketersediaan

Perpustakaan FK Nomor Panggil: N12.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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.

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