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Published March 2, 2012 | Published + Supplemental Material
Journal Article Open

Translation Elongation Regulates Substrate Selection by the Signal Recognition Particle


The signal recognition particle (SRP) is a universally conserved cellular machinery responsible for delivering membrane and secretory proteins to the proper cellular destination. The precise mechanism by which fidelity is achieved by the SRP pathway within the in vivo environment is yet to be understood. Previous studies have focused on the SRP pathway in isolation. Here we describe another important factor that modulates substrate selection by the SRP pathway: the ongoing synthesis of the nascent polypeptide chain by the ribosome. A slower translation elongation rate rescues the targeting defect of substrate proteins bearing mutant, suboptimal signal sequences both in vitro and in vivo. Consistent with a kinetic origin of this effect, similar rescue of protein targeting was also observed with mutant SRP receptors or SRP RNAs that specifically compromise the kinetics of SRP-receptor interaction during protein targeting. These data are consistent with a model in which ongoing protein translation is in constant kinetic competition with the targeting of the nascent proteins by the SRP and provides an important factor to regulate the fidelity of substrate selection by the SRP.

Additional Information

© 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, November 17, 2011, and in revised form, January 2, 2012. Published, JBC Papers in Press, January 6, 2012. This work was supported, in whole or in part, by National Institutes of Health Grant GM078024 (to S. S.). This article contains supplemental Figs. S1–S3. Supported by career awards from the Beckman Young Investigator Award, the Packard and Lucile Award in Science and Engineering, and the Henry Dreyfus Teacher-Scholar Award. We thank R. Hegde for RRL and microsomal membranes, H. Bernstein for the strain HDB52, J. Beckwith for antibodies, and X. Zhang and members of the Shan group for helpful comments on the manuscript.

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Published - Zhang2012p17580J_Biol_Chem.pdf

Supplemental Material - jbc.M111.325001-1.doc


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