Abstract B197: Translational control in macrophages during inflammatory response

Abstract

Translational control has been increasingly appreciated as a critical gene-regulatory mechanism during immune responses. Previous studies suggested that translation of select cytokines could be regulated by mRNA poly(A)-tail lengths in memory T-cells and macrophages. We carried out transcriptome-wide analysis with mRNA sequencing, ribosome-footprinting profiling as well as poly(A)-tail length profiling in both RAW264.7 cells and mouse thioglycollate-elicited peritoneal macrophages. No coupling between poly(A)-tail length and translational efficiency (TE) was observed in either cell type, arguing against a global translational-regulatory regime mediated by poly(A)-tail lengths. Immune activation with the treatment of lipopolysaccharides (LPS) to these cells did not change the uncoupled regime. Moreover, gene expression landscape in LPS-treated macrophages was dominated by mRNA level changes, with little contribution from TE changes. The up- or down-regulation of TE was not accompanied by concerted lengthening or shortening of poly(A) tails, implying existence of yet unclear translational control mechanisms in these immune cells. Finally, our studies in other biologic systems, including HeLa cells, Xenopus oocytes and yeast suggest that saturating levels of poly(A)-binding proteins might suppress poly(A) tail length-mediated translational control in various uncoupled systems, including immune cells. Citation Format: Kehui Xiang, David P. Bartel. Translational control in macrophages during inflammatory response [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B197.