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.