A methionine-Mettl3-N⁶-methyladenosine axis promotes polycystic kidney disease.

ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic disorder marked by numerous progressively enlarging kidney cysts. Mettl3, a methyltransferase that catalyzes the abundant N⁶-methyladenosine (m⁶A) RNA modification, is implicated in development, but its role in most diseases is unknown. Here, we show that Mettl3 and m⁶A levels are increased in mouse and human ADPKD samples and that kidney-specific transgenic Mettl3 expression produces tubular cysts. Conversely, Mettl3 deletion in three orthologous ADPKD mouse models slows cyst growth. Interestingly, methionine and S-adenosylmethionine (SAM) levels are also elevated in ADPKD models. Moreover, methionine and SAM induce Mettl3 expression and aggravate ex vivo cyst growth, whereas dietar

SUBMITTER: Ramalingam H 

PROVIDER: S-EPMC8172529 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature