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Interplay between signal sequence recognition and N‐terminal protein modification at the ribosome exit site
Author(s) -
Pool Martin,
Nyathi Yvonne,
Forte Gabriella,
Stirling Colin
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.542.2
Subject(s) - signal recognition particle , ribosome , signal peptide , endoplasmic reticulum , translocon , protein targeting , microbiology and biotechnology , a site , biology , translation (biology) , context (archaeology) , acetylation , chromosomal translocation , biochemistry , binding site , peptide sequence , rna , messenger rna , membrane protein , gene , paleontology , membrane
Proteins destined for secretion are targeted to the endoplasmic reticulum by N‐terminal signal sequences. In contrast, the majority of cytosolic proteins are modified at their extreme N‐termini by methionine‐aminopeptidase (MetAP) and/or N‐acetylation. Both of these processes typically occur co‐translationally soon after the nascent chain emerges from the ribosome exit site. Proteins targeted by the Signal Recognition Particle‐independent targeting pathway have a strong bias against N‐terminal processing and mutations that induce such processing inhibit translocation. Detailed examination of SRP‐dependent substrates reveals that mutations that induce N‐terminal processing have no effect on ER targeting. In the context of signal anchor proteins with a long N‐terminal cytoplasmic region, methionine processing and acetylation can occur, but has no effect on translocation. In contrast, signal anchor sequences with short N‐terminal regions are inefficiently processed at their N‐termini. This is rationalized by the finding that SRP and MetAP compete for a shared binding site on the ribosome. Furthermore, we find that additional ribosome‐associated factors regulate the differential recruitment of these two factors to secretory and cytosolic ribosome nascent chains. Hence a tightly regulated interplay exists to ensure the fidelity of the early events of nascent chain processing. This work is funded by the Biotechnology and Biological Sciences Research Council.