Meta-organization of Translation Centers Revealed by Proximity Mapping of Endoplasmic Reticulum Ribosome Interactors

The endoplasmic reticulum (ER) is a nexus for mRNA localization and translation; the molecular organization of these processes remains however largely undefined. To gain insight into mechanisms supporting a diverse ER translational landscape, we utilized BioID labeling to study the protein neighborhoods of the Sec61 translocon, specifically Sec61{beta}, an established ribosome interactor, and ER proteins (Ribophorin I, LRRC59, and Sec62) previously implicated in ribosome association. Divergent protein interactomes enriched for distinct GO functions were identified for the four reporters, within a cohort of shared interactors. Efficient BioID tagging of ribosomes was only observed for the Sec61{beta} and LRRC59 reporters. RNA-seq analyses of the Sec61{beta}- and LRRC59-labeled ribosomes revealed divergent enrichments in mRNAs and identified a transcriptome-wide role for the ER in proteome expression. These data provide evidence for a mesoscale organization of the ER and suggest that such organization provides a mechanism for the diversity of translation on the ER.