Figure 7. Model for let-767 RNAi blocking UPR^ER induction.

(A) Under WT condition, acyl-CoA metabolites are elongated by the let-767/HSD17B12 pathway and utilized at the membrane to synthesize other lipids such as neutral lipids stored in lipid droplets. IRE-1 responds to ER stress by splicing xbp-1u to xbp-1s, which is then translated and able to induce expression of the UPR^ER target genes (B) Knockdown of let-767 results in disequilibrium of let-767/HS17B12 pathway, leading to accumulation of intermediates such as 3-oxoacyl-CoA and reduced lipid production. Intermediate metabolites disrupt membrane quality (dashed line) and negatively affect induction of the UPR^ER by reducing splicing of xbp-1s (smaller arrows) by IRE-1 and reducing the function of xbp-1s post-splicing (smaller arrows).