Induction of an Alternative mRNA 5' Leader Enhances Translation of the Ciliopathy Gene Inpp5e and Resistance to Oncolytic Virus Infection

Hoang, Huy-Dung; Graber, Tyson; Jia, Jian-Jun; Vaidya, Nasana; Gilchrist, Victoria H; Xiang, Xiao; Li, Wencheng; Cowan, Kyle N; Gkogkas, Chistos G; Jaramillo, Maritza ORCID: https://orcid.org/0000-0002-1910-5684; Jafarnejad, Seyed Mehdi et Alain, Tommy (2019). Induction of an Alternative mRNA 5' Leader Enhances Translation of the Ciliopathy Gene Inpp5e and Resistance to Oncolytic Virus Infection Cell Reports , vol. 29 , nº 12. pp. 4010-4023. DOI: 10.1016/j.celrep.2019.11.072.

Prévisualisation

PDF - Version publiée Disponible sous licence Creative Commons Attribution. Télécharger (5MB) | Prévisualisation

Résumé

Residual cell-intrinsic innate immunity in cancer cells hampers infection with oncolytic viruses. Translational control of mRNA is an important feature of innate immunity, yet the identity of translationally regulated mRNAs functioning in host defense remains ill-defined. We report the translatomes 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 are translationally de-repressed mRNAs, including Inpp5e, encoding an inositol 5-phosphatase that modifies lipid second messenger signaling. We find that viral infection induces the 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 virus attachment. These findings uncover a role for translational control through alternative 5' leader expression and assign an antiviral function to the ciliopathy gene Inpp5e.

Type de document:	Article
Mots-clés libres:	INPP5E; RNA variant; alternative splicing; breast cancer; ciliopathy; isoform switch; oncolytic virus; ribosome profiling; translation; uORF
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	23 juill. 2021 17:16
Dernière modification:	15 févr. 2022 18:15
URI:	https://espace.inrs.ca/id/eprint/11603

Gestion Actions (Identification requise)

Modifier la notice