Sterol-Regulatory Binding Protein-1 (SREBP-1) mRNA contains an internal ribosome entry site that regulates its translation in response to cellular stress.

Sterol-regulatory-element-binding proteins (SREBPs) are a family of transcription factors that modulate the expression of several enzymes implicated in endogenous cholesterol, fatty acid, triacylglycerol and phospholipid synthesis. Here, evidences for SREBP-1 regulation at the translational level are reported. We demonstrated that the 5’-UTR (untranslated region) of the SREBP-1a mRNA contains an IRES (internal ribosome entry site). Cellular stress conditions, such as serum starvation caused an increase in the level of SREBP-1 precursor and mature form in Hep G2 cells, despite the overall reduction in protein synthesis, whereas mRNA level for SREBP-1 was unaffected by cellular stress. Transfection experiments carried out with a dicistronic construct demonstrated that the cap-dependent translation was affected more than IRES mediated translation by serum starvation. Unfolded protein response (UPR) also increased SREBP-1 expression in Hep G2 cells, through the capindependent translation mediated by IRES. Our fi ndings indicate that the presence of IRES in the SREBP-1a 5’-UTR allows translation to be maintained under conditions that are inhibitory to cap-dependent translation.