AI Article Synopsis
- The study investigates how Mettl3, an m(6)A transferase, regulates the transition from naïve to primed pluripotency in murine embryonic stem cells.
- Mettl3 knockout results in a lack of m(6)A modification in mRNAs, causing cells to struggle with terminating their naïve state and leading to abnormal lineage priming after implantation.
- The research emphasizes the importance of mRNA stability and the role of epigenetic modifications in regulating pluripotency states, ultimately contributing to early embryonic lethality when disrupted.
Article Abstract
Naïve and primed pluripotent states retain distinct molecular properties, yet limited knowledge exists on how their state transitions are regulated. Here, we identify Mettl3, an N(6)-methyladenosine (m(6)A) transferase, as a regulator for terminating murine naïve pluripotency. Mettl3 knockout preimplantation epiblasts and naïve embryonic stem cells are depleted for m(6)A in mRNAs, yet are viable. However, they fail to adequately terminate their naïve state and, subsequently, undergo aberrant and restricted lineage priming at the postimplantation stage, which leads to early embryonic lethality. m(6)A predominantly and directly reduces mRNA stability, including that of key naïve pluripotency-promoting transcripts. This study highlights a critical role for an mRNA epigenetic modification in vivo and identifies regulatory modules that functionally influence naïve and primed pluripotency in an opposing manner.
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| http://dx.doi.org/10.1126/science.1261417 | DOI Listing |
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