Dario F De Jesus, Zijie Zhang, Natalie K Brown, Xiaolu Li, Ling Xiao, Jiang Hu, Matthew J Gaffrey, Garrett Fogarty, Sevim Kahraman, Jiangbo Wei, Giorgio Basile, Tariq M Rana, Clayton Mathews, Alvin C Powers, Audrey V Parent, Mark A Atkinson, Sirano Dhe-Paganon, Decio L Eizirik, Wei-Jun Qian, Chuan He, Rohit N Kulkarni
Type 1 diabetes (T1D) is characterized by the destruction of pancreatic β-cells. Several observations have renewed the interest in β-cell RNA sensors and editors. Here, we report that N6 -methyladenosine (m6 A) is an adaptive β-cell safeguard mechanism that controls the amplitude and duration of the antiviral innate immune response at T1D onset. m6 A writer methyltransferase 3 (METTL3) levels increase drastically in β-cells at T1D onset but rapidly decline with disease progression. m6 A sequencing revealed the m6 A hypermethylation of several key innate immune mediators, including OAS1, OAS2, OAS3 and ADAR1 in human islets and EndoC-βH1 cells at T1D onset...
February 26, 2024: Nature Cell Biology