Mettl3-catalyzed m⁶A regulates histone modifier and modification expression in self-renewing somatic tissue.

ABSTRACT: N6-methyladenosine (m⁶A) is the most abundant modification on messenger RNAs (mRNAs) and is catalyzed by methyltransferase-like protein 3 (Mettl3). To understand the role of m⁶A in a self-renewing somatic tissue, we deleted Mettl3 in epidermal progenitors in vivo. Mice lacking Mettl3 demonstrate marked features of dysfunctional development and self-renewal, including a loss of hair follicle morphogenesis and impaired cell adhesion and polarity associated with oral ulcerations. We show that Mettl3 promotes the m⁶A-mediated degradation of mRNAs encoding critical histone modifying enzymes. Depletion of Mettl3 results in the loss of m⁶A on these mRNAs and increases their expression and associated modifications, resulting in wides

SUBMITTER: Maldonado Lopez AM 

PROVIDER: S-EPMC10854438 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature