RNA-binding protein DDX1 is responsible for fatty acid-mediated repression of insulin translation.

ABSTRACT: The molecular mechanism in pancreatic β cells underlying hyperlipidemia and insulin insufficiency remains unclear. Here, we find that the fatty acid-induced decrease in insulin levels occurs due to a decrease in insulin translation. Since regulation at the translational level is generally mediated through RNA-binding proteins, using RNA antisense purification coupled with mass spectrometry, we identify a novel insulin mRNA-binding protein, namely, DDX1, that is sensitive to palmitate treatment. Notably, the knockdown or overexpression of DDX1 affects insulin translation, and the knockdown of DDX1 eliminates the palmitate-induced repression of insulin translation. Molecular mechanism studies show that palmitate treatment causes DDX1 phosphorylation at S295 and dissociates DDX1 from insulin

SUBMITTER: Li Z 

PROVIDER: S-EPMC6294501 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature