The Insulin receptor and Insulin like growth factor receptor 5 UTRs support translation initiation independently of eIF4G1

Abstract

Protein synthesis is tightly regulated under stress conditions where energy may be scarce. Despite global repression of translation, some transcripts remain actively translated in order for the cell to be able to respond to the insult or prepare to quickly return normal cellular function after the stress ends. For the insulin receptor (Insr) and insulin-like growth factor receptor (Igf1r) transcripts this translation is mediated by an internal ribosome entry site (IRES) in their 5UTRs that functions independently of eukaryotic initiation factor 4A (eIF4A) and eIF4E. Here we show that these cellular IRESes are also able to promote translation independently of the scaffolding protein eIF4G1 both in vitro and in the cell. BackgroundIRES mediated translation initiation requires a different repertoire of factors than canonical cap-dependent translation. ResultsTreatments that inhibit the canonical translation factor eIF4G1 have little or no effect on the ability of the Insr and Igf1r cellular IRESes to promote translation. ConclusionTranscripts for two cellular receptors contain RNA elements that facilitate translation initiation without intact eIF4G1 SignificanceCellular IRES mechanisms may resemble viral type III IRESes allowing them to promote translate with a limited number of initiation factors allowing them to work under stress conditions when canonical translation is repressed.