METTL14 Regulates Intestine Cellular Senescence through m(6)A Modification of Lamin B Receptor

N-6-Methyladenosine (m(6)A) modification is involved in multiple biological processes including aging. However, the regulation of m(6)A methyltransferase-like 14 (METTL14) in aging remains unclear. Here, we revealed that the level of m(6)A modification and the expression of METTL14 were particularly decreased in the intestine of aged mice as compared to young mice. Similar results were confirmed in Drosophila melanogaster. Knockdown of Mettl14 in Drosophila resulted in a short lifespan, associated disrupted intestinal integrity, and reduced climbing ability. In human CCD-18Co cells, knockdown of METTL14 accelerated cellular senescence, and the overexpression of METTL14 rescued senescent phenotypes. We also identified the lamin B receptor (LBR) as a target gene for METTL14-mediated m(6)A modification. Knockdown of METTL14 decreased m(6)A level of LBR, resulted in LBR mRNA instability, and thus induced cellular senescence. Our findings suggest that METTL14 plays an essential role in the m(6)A modification-dependent aging process via the regulation of LBR and provides a potential target for cellular senescence.