Translatomic analysis of the wild-type (WT) and total body eIF2A-KO mouse liver tissue

The heterotrimeric factor eIF2 (α, β, γ) is the primary mediator of methionyl-initiator tRNA (Met-tRNAi) delivery to the 40S ribosomal subunit. eIF2A is an alternative factor capable of mediating this delivery and is thought to function in non-canonical translation initiation pathways. To investigate the physiological role of eIF2A in mammals, our laboratory generated a total eIF2A knockout (KO) mouse model.

Although eIF2A-KO mice are viable, they exhibit features of metabolic syndrome. To examine translatomic alterations associated with eIF2A deficiency, we performed ribosome profiling on liver tissues from wild-type (WT) and eIF2A-KO mice. High-throughput sequencing was used to identify affected molecular pathways and to define the role of eIF2A in metabolic homeostasis.