CBP80 orchestrates co-translational protein targeting to endoplasmic reticulum.

Eukaryotic membrane and secretory proteins, destined to endoplasmic reticulum (ER),must be targeted to appropriated cellular location for their protein synthesis. Sincemistargeting of proteins caused cellular stress and defect, multiple molecularmechanisms for ER targeting have been developed. Among them, signal recognitionparticle (SRP) regulates ER-targeting of proteins in a translation dependent manners.However, the molecular details of mechanisms remain unclear. Here, we identify thatnuclear cap binding protein 80, pioneer round of translation initiation factor, isrequired for delivery of proteins to ER through direct interaction of SRP54, acomponent of SRP complex. Our genome-wide analysis also shows CBP80-boundmRNP complex accumulated after downregulation of SRP receptors. Furthermore, ER-targeted proteins were mistargeted to other cellular location under CBP80 depletedcondition. Collectively, our data provides an insight into CBP80 function in theregulation of SRP-meditated ER targeting pathway.