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The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity.
- Source :
- Nature; 3/11/2021, Vol. 591 Issue 7849, p322-326, 5p
- Publication Year :
- 2021
-
Abstract
- The RNA modification N<superscript>6</superscript>-methyladenosine (m<superscript>6</superscript>A) has critical roles in many biological processes1,2. However, the function of m<superscript>6</superscript>A in the early phase of mammalian development remains poorly understood. Here we show that the m<superscript>6</superscript>A reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required for the maintenance of mouse embryonic stem (ES) cells in an m<superscript>6</superscript>A-dependent manner, and that its deletion initiates cellular reprogramming to a 2C-like state. Mechanistically, YTHDC1 binds to the transcripts of retrotransposons (such as intracisternal A particles, ERVK and LINE1) in mouse ES cells and its depletion results in the reactivation of these silenced retrotransposons, accompanied by a global decrease in SETDB1-mediated trimethylation at lysine 9 of histone H3 (H3K9me3). We further demonstrate that YTHDC1 and its target m<superscript>6</superscript>A RNAs act upstream of SETDB1 to repress retrotransposons and Dux, the master inducer of the two-cell stage (2C)-like program. This study reveals an essential role for m<superscript>6</superscript>A RNA and YTHDC1 in chromatin modification and retrotransposon repression.N<superscript>6</superscript>-methyladenosine RNA and its reader YTHDC1 serve as a bridge to silencing retrotransposons through the RNA derived from these retrotransposons in mouse ES cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 591
- Issue :
- 7849
- Database :
- Complementary Index
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 149160924
- Full Text :
- https://doi.org/10.1038/s41586-021-03313-9