Genes encode proteins and proteins dictate cell fate. Messenger RNAs (mRNA) act as templates for protein synthesis. Therefore, appropriate regulation of mRNA is central to the function of eukaryotic cells. One potential regulatory mechanism of mRNA is through mRNA modification. Recent studies showed that tens of thousands mRNA and noncoding RNA molecules in mammalian cells are tagged with a specific type of chemical modification, named N6-methyladenosine or m6A. Excess m6A in mouse leads to infertility. However, how m6A exerts these functions is unknown.
Recently, my lab identified a protein complex that governs m6A formation. Depleting such complex in mouse embryonic stem cells leads to cellular differentiation. Significantly, we discovered that m6A shortens the half-life of a subset of mRNAs, including mRNAs encoding pro-differentiation genes. These findings suggested that the major function of m6A in mammalian cells is to destabilize RNA and demonstrated an essential role of m6A in keeping pluripotent cells undifferentiated.
Currently, we are digging deeper into the molecular mechanisms through which m6A regulates RNA stability. We are also investigating how m6A regulates mESC ground state and whether m6A plays a role in mESC differentiation. We welcome applications from students and postdoctoral fellows interested in these research areas.