SRP orchestrates protein biogenesis beyond initial ER-membrane targeting

However, its range of substrates and point of engagement during targeting, and hence full biological impact remain unclear. Here, we examined SRP interactions with the nascent proteome of S. cerevisiae during translation and membrane targeting.

SRP binds effectively to transmembrane domains (TMDs) as they emerge from the ribosomal tunnel, but not to most cleavable signal peptides. We identify nascent chain features that promote SRP binding, allowing to develop a predictive algorithm. We show SRP performs a role in triaging nascent ER proteins into distinct targeting routes and downstream maturation processes.