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Visualization of Endoplasmic Reticulum Localized mRNAs in Mammalian Cells
Published on: December 17, 2012
SRP orchestrates protein biogenesis beyond initial ER membrane targeting.
Ilgın Eser Kotan1, Sabrina Sartori1, Rudra Bose1,2
1Center for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.
Nature Communications
|June 16, 2026
Summary
The Signal Recognition Particle (SRP) binds transmembrane domains during protein synthesis, guiding ER targeting. It also helps ribosomes re-engage the translocon for multipass membrane protein biogenesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Biogenesis
Background:
- The Signal Recognition Particle (SRP) pathway is crucial for targeting proteins to the endoplasmic reticulum (ER).
- The precise mechanisms and scope of SRP involvement in targeting diverse proteins, including membrane proteins, are not fully understood.
- Understanding SRP interactions is key to deciphering protein translocation and maturation processes.
Purpose of the Study:
- To investigate Signal Recognition Particle (SRP) interactions with the nascent proteome during translation and membrane targeting in Saccharomyces cerevisiae.
- To identify features of nascent proteins that influence SRP binding and to explore SRP's role in protein triage and maturation.
- To elucidate the mechanisms of SRP-mediated targeting for multipass membrane proteins.
Main Methods:
- Analysis of SRP interactions with nascent polypeptides emerging from ribosomes.
- Identification of sequence and structural features promoting SRP binding using a predictive algorithm.
- Investigating ribosome-membrane dissociation and chaperone-assisted folding during protein translocation.
- Studying the retargeting of ribosomes translating multipass membrane proteins.
Main Results:
- SRP effectively binds transmembrane domains (TMDs) as they exit the ribosome, with limited binding to signal peptides.
- A predictive algorithm was developed based on identified nascent chain features that promote SRP binding.
- SRP plays a role in sorting nascent ER proteins into distinct targeting pathways and maturation routes.
- Ribosomes can dissociate from the membrane before translocation completion, with Ssb chaperone assisting folding.
- Repeated SRP interactions with internal TMDs facilitate the retargeting of ribosomes for multipass membrane protein synthesis.
Conclusions:
- SRP binding to emerging TMDs is a primary mechanism for initiating ER targeting.
- SRP acts as a crucial triage factor, directing proteins to specific translocation and maturation pathways.
- Chaperone collaboration with SRP is essential for efficient biogenesis of complex membrane proteins.
- The findings provide new insights into the dynamic interplay between SRP, ribosomes, chaperones, and the translocon during protein biogenesis.
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