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Science. 2018 Feb 9;359(6376):689-692. doi: 10.1126/science.aar3607. Epub 2018 Jan 18.

Defining the physiological role of SRP in protein-targeting efficiency and specificity.

Author information

1
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.
2
Department of Molecular and Cellular Biology, University of California, Davis, CA, USA.
3
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA. jonathan.weissman@ucsf.edu.
4
Howard Hughes Medical Institute, University of California, San Francisco, CA, USA.

Abstract

The signal recognition particle (SRP) enables cotranslational delivery of proteins for translocation into the endoplasmic reticulum (ER), but its full in vivo role remains incompletely explored. We combined rapid auxin-induced SRP degradation with proximity-specific ribosome profiling to define SRP's in vivo function in yeast. Despite the classic view that SRP recognizes amino-terminal signal sequences, we show that SRP was generally essential for targeting transmembrane domains regardless of their position relative to the amino terminus. By contrast, many proteins containing cleavable amino-terminal signal peptides were efficiently cotranslationally targeted in SRP's absence. We also reveal an unanticipated consequence of SRP loss: Transcripts normally targeted to the ER were mistargeted to mitochondria, leading to mitochondrial defects. These results elucidate SRP's essential roles in maintaining the efficiency and specificity of protein targeting.

PMID:
29348368
PMCID:
PMC5970945
DOI:
10.1126/science.aar3607
[Indexed for MEDLINE]
Free PMC Article

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