GSE137757 Induction of an alternative 5' leader enhances translation of Inpp5e and resistance to oncolytic virus infection

Contributors : Huy-Dung Hoang ; Tyson E Graber ; Tommy Alain ; Seyed M JafarnejadSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusResidual cell-intrinsic innate immunity in cancer cells hampers infection with oncolytic viruses. Control of mRNA translation is an important feature of innate immunity, yet the identity of mRNA substrates that participate in host defences remain ill-defined. We characterized the translatome of resistant murine “4T1” breast cancer cells infected with three of the most clinically advanced oncolytic viruses: Herpes Simplex virus 1, Reovirus and Vaccinia virus. Common among all three infections were translationally de-repressed mRNAs including Inpp5e, encoding an inositol 5-phosphatase that modifies lipid second messenger signalling. We found that viral infection induced expression of an Inpp5e mRNA variant that lacks repressive upstream open reading frames (uORFs) within its 5’ leader and is efficiently translated. Furthermore, we show that INPP5E contributes to antiviral immunity by altering vir us attachment. These findings uncover a role for translational control through alternative 5’ leader expression and assign an antiviral function to the ciliopathy gene INPP5E.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research