Disome and trisome profiling reveal targets of ribosome quality control
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA578122 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10302100.fastq.gz | Fastqsanger.gz | |||
| SRR10302101.fastq.gz | Fastqsanger.gz | |||
| SRR10302102.fastq.gz | Fastqsanger.gz | |||
| SRR10302103.fastq.gz | Fastqsanger.gz | |||
| SRR10302104.fastq.gz | Fastqsanger.gz |
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Project description:The ribosome-associated protein quality control (RQC) system that resolves stalled translation events is activated when ribosomes collide and form disome, trisome or higher order complexes. However, it is unclear whether this system distinguishes collision complexes formed on defective mRNAs from those with functional roles on endogenous transcripts. Here, we performed disome and trisome footprint profiling in yeast and found collisions were enriched on diverse sequence motifs known to slow translation. When 60S recycling was inhibited, disomes accumulated at stop codons and could move into the 3’UTR to reinitiate translation. The ubiquitin ligase and RQC factor Hel2/ZNF598 generally recognized collisions but did not trigger degradation of endogenous transcripts. However, loss of Hel2 triggered the integrated stress response, via phosphorylation of eIF2alpha, thus linking these pathways. Our results suggest that Hel2 has a role in sensing ribosome collisions on endogenous mRNAs and such events may be important for cellular homeostasis.
2020-05-26 | GSE139036 | GEO
Project description:The ribosome-associated protein quality control (RQC) system that resolves stalled translation events is activated when ribosomes collide and form disome, trisome, or higher-order complexes. However, it is unclear whether this system distinguishes collision complexes formed on defective mRNAs from those with functional roles on endogenous transcripts. Here, we performed disome and trisome footprint profiling in yeast and found collisions were enriched on diverse sequence motifs known to slow translation. When 60S recycling was inhibited, disomes accumulated at stop codons and could move into the 3' UTR to reinitiate translation. The ubiquitin ligase and RQC factor Hel2/ZNF598 generally recognized collisions but did not induce degradation of endogenous transcripts. However, loss of Hel2 triggered the integrated stress response, via phosphorylation of eIF2α, thus linking these pathways. Our results suggest that Hel2 has a role in sensing ribosome collisions on endogenous mRNAs, and such events may be important for cellular homeostasis.
| S-EPMC7484464 | biostudies-literature
Project description:In protein synthesis, ribosome movement is not always smooth, rather often impeded by numerous reasons. Although the deceleration of ribosome defines the fates of the mRNAs and the synthesizing proteins, fundamental questions remain to be addressed including where ribosomes pause in mRNAs, what kind of RNA/amino acid context causes the pausing, and how physiologically significant the slowdown of protein synthesis is. Here we surveyed the position of ribosome collisions, caused by ribosome pausing, at a genome-wide level using the modified ribosome profiling in human and zebrafish. The collided ribosomes, i.e. disome, emerge at various sites; the proline-proline-lysine motif, stop codons, and 3′ UTR. The number of ribosomes in a collision is not limited to two, rather four to five, forming a queue of ribosomes. Especially, XBP1, a key modulator of unfolded protein response, shows striking queues of collided ribosomes thus acts as a substrate for ribosome-associated quality control (RQC) to avoid the accumulation of undesired proteins in the absence of stress. Our results provide an insight into the causes and the consequences of ribosome slowdowns by dissecting the specific architecture of ribosomes.
2020-05-05 | GSE133393 | GEO
Project description:The ribosome-associated quality control (RQC) is a surveillance system for aberrant translation, sensing ribosome collisions. Although the molecular mechanism has been extensively studied, the endogenous targets of RQC in human cells were poorly understood. Here, starting from the study of codon specificity of eukaryotic termination factor eRF1, we unexpectedly find that misrecognition of UUA sense codon by eRF1 leads to ribosome collisions and provides the source of RQC substrates in humans. eRF1-selective Monosome-Seq and Disome-Seq reveal that eRF1 recruitment to ribosome was not restricted to the stop codons but also the sub-cognate sense codons, including the UUA codon. The UUA misrecognition by eRF1 causes ribosome collision without termination reaction. Remarkably, Disome-Seq with the depletion of ASCC3 and 4EHP, key factors in RQC, showed that ribosome stalled at UUA codons are the predominant sub-populations rescued by RQC. Failure to resolve ribosome collisions by RQC triggers p38 phosphorylation and upregulation of stress response transcription factor ATF3. This study presents the impact of sense codon misrecognition by the termination factor on translation homeostasis in human cells.
2024-09-18 | GSE275336 | GEO
Project description:Genome-wide survey of ribosome collision [monosome/disome]
| PRJNA551384 | ENA
Project description:Ubiquitination of Stalled Ribosome Triggers Ribosome-associated Quality Control
| PRJNA356322 | ENA
Project description:Ribosomes that stall before completing peptide synthesis must be recycled and returned to the cytoplasmic pool. The protein Dom34 and cofactors Hbs1 and Rli1 can dissociate stalled ribosomes in vitro, but the identity of targets in the cell is unknown. Here we use ribosome profiling methodology to reveal a high- resolution molecular characterization of Dom34 function in vivo. We show that Dom34 removes stalled ribosomes from mRNAs that are truncated but, in contrast, does not generally dissociate ribosomes on coding sequences known to trigger stalling, such as polyproline. We also show that Dom34 targets arrested ribosomes near the ends of 3 ? UTRs. These ribosomes appear to gain access to the 3 ? UTR via a mechanism that does not require decoding of the mRNA. These results suggest that Dom34 carries out the important task of rescuing ribosomes found in noncoding regions. 25 samples are included in the study (2 mRNA-Seq samples and 23 ribosome footprint profiling samples). These include wild-type and dom34 or hbs1 knockout strains that were created in a variety of genetic backgrounds, treated with various agents in cell culture (e.g. diamide, 3-AT, or glucose starvation), treated differently during cell lysis (use of cycloheximide vs. other ribosome-stabilizing agents), or prepared in different ways after cell lysis (e.g. retention of short vs. long monosome-protected footprints or disome footprints).
2013-12-19 | E-GEOD-52968 | biostudies-arrayexpress
Project description:Genome-wide detection of monosome and disome distributions in yeast cells
2020-12-10 | GSE158572 | GEO
Project description:Translation elongation stalling has the potential to produce toxic truncated protein fragments. Translation of either non-stop mRNA or transcripts coding for poly-basic sequences induces ribosome stalling, and the arrest product is degraded by the ribosome-mediated quality control (RQC) system. During this process, the stalled ribosome is dissociated into subunits, and the polypeptide is ubiquitinated by the E3 ubiquitin ligase Listerin on the 60S large ribosomal subunit, leading to subsequent proteasomal degradation. However, it is largely unknown how the specific stalled ribosomes are recognized as aberrant to engage the RQC system. Here, we report that ubiquitination of the ribosomal protein uS10 of the 40S small ribosomal subunit, by the E3 ubiquitin ligase Hel2 (or RQC-trigger (Rqt) 1) initiates RQC. We identified a novel RQC-trigger (RQT) complex composed of the RNA helicase-family protein Slh1/Rqt2, the ubiquitin binding protein Cue3/Rqt3, and yKR023W/Rqt4 that is required for RQC. The defects in RQC of the RQT mutants correlated with sensitivity to anisomycin, which stalls ribosome at the rotated form, suggesting that RQT factors rescue ribosomes stalled by this drug. Our un-biased survey by ribosome profiling revealed that ribosomes stalled at the rotated state with specific pairs of codons at P-A sites serve as RQC substrates. Rqt1 specifically ubiquitinates these arrested ribosomes to target them to the RQT complex, allowing subsequent RQC reactions including dissociation of the stalled ribosome into subunits. Our results provide mechanistic insight into the surveillance system for aberrant proteins induced by ribosome stalling and mediated by ribosome ubiquitination.
2017-07-31 | GSE90919 | GEO
Project description:Distinct ribosome states trigger diverse mRNA quality control pathways
| PRJNA782905 | ENA