Interaction of methionine sulfoxide reductase B5 with SlMYC2 stimulates the transcription of MeJA-mediated autophagy-related genes in tomato fruit

Methyl jasmonate(MeJA)has been shown to induce autophagy in various plant stress responses and metabolic pathways.MYC2 is involved in MeJA-mediated postharvest fruit biological metabolism,but it is unclear how it affects MeJA-induced fruit autophagy.In this study,we noticed that silencing SlMYC2 significantly reduced the increase in autophagy-related genes(SlATGs)expression induced by MeJA.SlMYC2 could also bind to the promoters of several SlATGs,including SlATG13a,SlATG13b,SlATG18a,and SlATG18h,and activate their transcript levels.Moreover,SlMsrB5,a methionine sulfoxide reductase,could interact with SlMYC2.Methionine oxidation in SlMYC2 and mimicking sulfoxidation in SlMYC2 by mutation of methionine-542 to glutamine reduced the DNA-binding ability and transcriptional activity of SlMYC2,respectively.SlMsrB5 partially repaired oxidized SlMYC2 and restored its DNA-binding ability.On the other hand,silencing SlMsrB5 inhibited the transcript levels of SlMYC2-targeted genes(SlATG13a,SlATG13b,SlATG18a,and SlATG18h).Similarly,dual-luciferase reporter(DLR)analysis revealed that SlMsrB5–SlMYC2 interaction significantly increased the ability of SlMYC2-mediated transcriptional activation of SlATG13a,SlATG13b,SlATG18a,and SlATG18h.These findings demonstrate that SlMsrB5-mediated cyclic oxidation/reduction of methionine in SlMYC2 inf luences SlATGs expression.Collectively,these findings reveal the mechanism of SlMYC2 in SlATGs transcriptional regulation,providing insight into the mechanism of MeJA-mediated postharvest fruit quality regulation.

Promotion of nonalcoholic steatohepatitis by RNA N^(6)-methyladenosine reader IGF2BP2 in mice

Nonalcoholic steatohepatitis(NASH)has emerged as the major cause of end-stage liver diseases.However,an incomplete understanding of its molecular mechanisms severely dampens the development of pharmacotherapies.In the present study,through systematic screening of genome-wide mRNA expression from three mouse models of hepatic inflammation and fibrosis,we identified IGF2BP2,an N6-methyladenosine modification reader,as a key regulator that promotes NASH progression in mice.Adenovirus or adeno-associated virus-mediated overexpression of IGF2BP2 could induce liver steatosis,inflammation,and fibrosis in mice,at least in part,by increasing Tab2 mRNA stability.Besides,hepatic overexpression of IGF2BP2 mimicked gene expression profiles and molecular pathways of human NASH livers.Of potential clinical significance,IGF2BP2 expression is significantly upregulated in the livers of NASH patients.Moreover,knockdown of IGF2BP2 substantially alleviated liver injury,inflammation,and fibrosis in diet-induced NASH mice.Taken together,our findings reveal an important role of IGF2BP2 in NASH,which may provide a new therapeutic target for the treatment of NASH.