Shiber et al. 2018 (PRJNA479682)

General Details

Title Cotranslational assembly of protein complexes in eukaryotes revealed by ribosome profiling
Organism
Number of Samples 90
Release Date 2018/07/03 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP152018
ENA SRP152018
GEO GSE116570
BioProject PRJNA479682

Publication

Title
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)
SRR7471227 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471228 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471229 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471230 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471231 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471232 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471233 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471234 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471235 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471236 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471237 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471238 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471239 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471240 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471241 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471242 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471243 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471244 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471245 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471246 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471247 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471248 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471249 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471250 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471251 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471252 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471253 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471254 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471255 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471256 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471257 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471258 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471259 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471260 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471261 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471262 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471263 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471264 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471265 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471266 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471267 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471268 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471269 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471270 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471271 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471272 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471273 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471274 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471275 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471276 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471277 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471278 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471279 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471280 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471281 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471282 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471283 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471284 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471285 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471286 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471287 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471288 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471289 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471290 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471291 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471292 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471293 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471294 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471295 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471296 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471297 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471298 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471299 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471300 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471301 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471302 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471303 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471304 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471305 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471306 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471307 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471308 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471309 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471310 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471311 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471312 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471313 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471314 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471315 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
SRR7471316 PRJNA479682 Saccharomyces cerevisiae 0.0 0.0 0.0
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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