A methionine-Mettl3-N6-methyladenosine axis promotes polycystic kidney disease.
作者： Patricia Cobo-Stark , Jair M. Espindola-Netto , Sachin Hajarnis , Sonu Kashyap , Chao Xing
DOI: 10.1016/J.CMET.2021.03.024
关键词: Polycystic kidney disease 、 N6-Methyladenosine 、 Endocrinology 、 Cyst 、 Internal medicine 、 Biology 、 Methyltransferase 、 Kidney cysts 、 Methionine 、 Transgene 、 Autosomal dominant polycystic kidney disease
摘要: Summary Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic disorder marked by numerous progressively enlarging cysts. Mettl3, methyltransferase that catalyzes the abundant N6-methyladenosine (m6A) RNA modification, implicated in development, but its role most diseases unknown. Here, we show Mettl3 and m6A levels are increased mouse human ADPKD samples kidney-specific transgenic expression produces tubular Conversely, deletion three orthologous models slows cyst growth. Interestingly, methionine S-adenosylmethionine (SAM) also elevated models. Moreover, SAM induce aggravate ex vivo growth, whereas dietary restriction attenuates ADPKD. Finally, activates cyst-promoting c-Myc cAMP pathways through enhanced Avpr2 mRNA modification translation. Thus, promotes links utilization to epitranscriptomic activation of proliferation
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