AI Article Synopsis
- Embryos can enter a reversible state called diapause in response to unfavorable environmental conditions, but the mechanisms behind this process are not well understood.
- Research shows that the RNA methylation enzyme Mettl3 is essential for maintaining developmental dormancy in mouse embryonic stem cells and blastocysts by destabilizing certain mRNAs.
- Mettl3 influences this dormancy through two main processes: it destabilizes global mRNA and inhibits transcription by affecting the mRNA of the transcriptional amplifier N-Myc, linking transcriptomic and epitranscriptomic regulation.
Article Abstract
Embryos across metazoan lineages can enter reversible states of developmental pausing, or diapause, in response to adverse environmental conditions. The molecular mechanisms that underlie this remarkable dormant state remain largely unknown. Here we show that m A RNA methylation by Mettl3 is required for developmental pausing in mice by maintaining dormancy of paused embryonic stem cells and blastocysts. Mettl3 enforces transcriptional dormancy via two interconnected mechanisms: i) it promotes global mRNA destabilization and ii) suppresses global nascent transcription by specifically destabilizing the mRNA of the transcriptional amplifier and oncogene N-Myc, which we identify as a critical anti-pausing factor. Our findings reveal Mettl3 as a key orchestrator of the crosstalk between transcriptomic and epitranscriptomic regulation during pausing, with implications for dormancy in stem cells and cancer.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915470 | PMC |
| http://dx.doi.org/10.1101/2023.01.30.526234 | DOI Listing |
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