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Published October 7, 2019 | Published + Supplemental Material
Journal Article Open

A molecular recognition feature mediates ribosome-induced SRP-receptor assembly during protein targeting


Molecular recognition features (MoRFs) provide interaction motifs in intrinsically disordered protein regions to mediate diverse cellular functions. Here we report that a MoRF element, located in the disordered linker domain of the mammalian signal recognition particle (SRP) receptor and conserved among eukaryotes, plays an essential role in sensing the ribosome during cotranslational protein targeting to the endoplasmic reticulum. Loss of the MoRF in the SRP receptor (SR) largely abolishes the ability of the ribosome to activate SRP-SR assembly and impairs cotranslational protein targeting. These results demonstrate a novel role for MoRF elements and provide a mechanism for the ribosome-induced activation of the mammalian SRP pathway. Kinetic analyses and comparison with the bacterial SRP further suggest that the SR MoRF functionally replaces the essential GNRA tetraloop in the bacterial SRP RNA, providing an example for the replacement of RNA function by proteins during the evolution of ancient ribonucleoprotein particles.

Additional Information

© 2019 Hwang Fu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). Submitted: January 1, 2019. Revision received June 28, 2019. Accepted: August 26, 2019. Published September 19, 2019. We thank the Shan laboratory members for valuable suggestions and H. Bernstein for sharing canine pancreatic microsomes. This work was supported by National Institutes of Health grant GM078024 and Gordon and Betty Moore Foundation GBMF2939 to S.-o. Shan. The authors declare no competing financial interests. Author contributions: Y.-H. Hwang Fu and S.-o. Shan designed research; Y.-H. Hwang Fu, S. Chandrasekar, and S.-o. Shan performed research; Y.-H. Hwang Fu, S. Chandrasekar, and J.H. Lee contributed new reagents/analytic tools; Y.-H. Hwang Fu, S. Chandrasekar, and S.-o. Shan analyzed data; Y.-H. Huang Fu and S.-o. Shan wrote the paper; S.-o. Shan supervised the project.

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Supplemental Material - JCB_201901001_sm.pdf


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