A LINE1-Nucleolin partnership regulates early development and ESC identity

Michelle Percharde, Chih-Jen Lin, Yafei Yin, Juan Guan, Gabriel A Peixoto, Aydan Bulut-Karslioglu, Steffen Biechele, Bo Huang, Xiaohua Shen, Miguel Ramalho-Santos

Research output: Contribution to journalArticlepeer-review

Abstract

Transposable elements represent nearly half of mammalian genomes and are generally described as parasites, or “junk DNA.” The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, yet it is paradoxically highly expressed during early development. Here, we report that LINE1 plays essential roles in mouse embryonic stem cells (ESCs) and pre-implantation embryos. In ESCs, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a transcriptional program specific to the 2-cell embryo. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, promoting rRNA synthesis and ESC self-renewal. In embryos, LINE1 RNA is required for Dux silencing, synthesis of rRNA, and exit from the 2-cell stage. The results reveal an essential partnership between LINE1 RNA, Nucleolin, Kap1, and peri-nucleolar chromatin in the regulation of transcription, developmental potency, and ESC self-renewal.
Original languageEnglish
Pages (from-to)391-405.e19
Number of pages23
JournalCell
Volume174
Issue number2
Early online date21 Jun 2018
DOIs
Publication statusPublished - 12 Jul 2018

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