N⁶-adenosine methylation controls the translation of insulin mRNA.

ABSTRACT: Control of insulin mRNA translation is crucial for energy homeostasis, but the mechanisms remain largely unknown. We discovered that insulin mRNAs across invertebrates, vertebrates and mammals feature the modified base N⁶-methyladenosine (m⁶A). In flies, this RNA modification enhances insulin mRNA translation by promoting the association of the transcript with polysomes. Depleting m⁶A in Drosophila melanogaster insulin 2 mRNA (dilp2) directly through specific 3' untranslated region (UTR) mutations, or indirectly by mutating the m⁶A writer Mettl3, decreases dilp2 protein production, leading to aberrant energy homeostasis and diabetic-like phenotypes. Together, our findings reveal adenosine mRNA methylation as a key regulator of insulin protein syn

SUBMITTER: Wilinski D 

PROVIDER: S-EPMC11756593 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature