Eukaryotic Initiation Factor 5A2 Regulates Expression of Antiviral Genes

Translation factors are essential for regulation of protein synthesis. The eukaryotic translation initiation factor 5A (eIF5A) family is made up of two paralogues - eIF5A1 and eIF5A2 - which display high sequence homology but distinct tissue tropism. While eIF5A1 directly binds to the ribosome and regulates translation initiation, elongation, and termination, the molecular function of eIF5A2 remains poorly understood. Here, we engineer an eIF5A2 knockout allele in the SW480 colon cancer cell line. Using ribosome profiling and RNA-Sequencing, we reveal that eIF5A2 is functionally distinct from eIF5A1 and does not regulate transcript-specific or global protein synthesis. Instead, eIF5A2 knockout leads to decreased intrinsic antiviral gene expression, including members of the IFITM and APOBEC3 family. Furthermore, cells lacking eIF5A2 display increased permissiveness to virus infection. Our results uncover eIF5A2 as a factor involved regulating the antiviral transcriptome, and reveal an example of how gene duplications of translation factors can result in proteins with distinct functions. (C) 2022 The Author(s). Published by Elsevier Ltd.

Automated summary

Translation factors play a crucial role in protein synthesis regulation. This study reveals that eIF5A2, a member of the eukaryotic translation initiation factor 5A family, functions differently from eIF5A1. It is not involved in transcript-specific or global protein synthesis regulation, but instead regulates antiviral gene expression. Cells lacking eIF5A2 are more susceptible to virus infection. This research uncovers the functional distinction of eIF5A2 and provides an example of gene duplications resulting in proteins with distinct functions.