Shiber et al. 2018 (PRJNA479682)
General Details
Title | Cotranslational assembly of protein complexes in eukaryotes revealed by ribosome profiling |
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Organism | |
Number of Samples | 90 |
Release Date | 2018/07/03 00:00 |
Sequencing Types | |
Protocol Details |
Study Links
GWIPS-viz | Trips-Viz |
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Repository Details
SRA | SRP152018 |
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ENA | SRP152018 |
GEO | GSE116570 |
BioProject | PRJNA479682 |
Publication
Title | |
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Authors | Shiber A,Döring K,Friedrich U,Klann K,Merker D,Zedan M,Tippmann F,Kramer G,Bukau B |
Journal | Nature |
Publication Date | 2018 Sep |
Abstract | The folding of newly synthesized proteins to the native state is a major challenge within the crowded cellular environment, as non-productive interactions can lead to misfolding, aggregation and degradation 1 . Cells cope with this challenge by coupling synthesis with polypeptide folding and by using molecular chaperones to safeguard folding cotranslationally 2 . However, although most of the cellular proteome forms oligomeric assemblies 3 , little is known about the final step of folding: the assembly of polypeptides into complexes. In prokaryotes, a proof-of-concept study showed that the assembly of heterodimeric luciferase is an organized cotranslational process that is facilitated by spatially confined translation of the subunits encoded on a polycistronic mRNA 4 . In eukaryotes, however, fundamental differences-such as the rarity of polycistronic mRNAs and different chaperone constellations-raise the question of whether assembly is also coordinated with translation. Here we provide a systematic and mechanistic analysis of the assembly of protein complexes in eukaryotes using ribosome profiling. We determined the in vivo interactions of the nascent subunits from twelve hetero-oligomeric protein complexes of Saccharomyces cerevisiae at near-residue resolution. We find nine complexes assemble cotranslationally; the three complexes that do not show cotranslational interactions are regulated by dedicated assembly chaperones 5-7 . Cotranslational assembly often occurs uni-directionally, with one fully synthesized subunit engaging its nascent partner subunit, thereby counteracting its propensity for aggregation. The onset of cotranslational subunit association coincides directly with the full exposure of the nascent interaction domain at the ribosomal tunnel exit. The action of the ribosome-associated Hsp70 chaperone Ssb 8 is coordinated with assembly. Ssb transiently engages partially synthesized interaction domains and then dissociates before the onset of partner subunit association, presumably to prevent premature assembly interactions. Our study shows that cotranslational subunit association is a prevalent mechanism for the assembly of hetero-oligomers in yeast and indicates that translation, folding and the assembly of protein complexes are integrated processes in eukaryotes. |
PMC | PMC6372068 |
PMID | 30158700 |
DOI |
Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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SRR7471227 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471228 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471229 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471230 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471231 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471232 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471233 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471234 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471235 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471236 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471237 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471238 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471239 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471240 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471241 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471242 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471243 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471244 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471245 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471246 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471247 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471248 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471249 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471250 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471251 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471252 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471253 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471254 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471255 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471256 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471257 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471258 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471259 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471260 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471261 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471262 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471263 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471264 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471265 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471266 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471267 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471268 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471269 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471270 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471271 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471272 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471273 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471274 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471275 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471276 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471277 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471278 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471279 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471280 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471281 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471282 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471283 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471284 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471285 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471286 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471287 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471288 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471289 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471290 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471291 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471292 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471293 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471294 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471295 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471296 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471297 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471298 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471299 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471300 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471301 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471302 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471303 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471304 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471305 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471306 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471307 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471308 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471309 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471310 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471311 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471312 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471313 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471314 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471315 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
SRR7471316 | PRJNA479682 | Saccharomyces cerevisiae | |||||||||||
Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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