Sensing of individual stalled 80S ribosomes by Fap1 for nonfunctional rRNA turnover

Li, Sihan; Ikeuchi, Ken; Kato, Masatane; Buschauer, Robert; Sugiyama, Takato; Adachi, Shungo; Kusano, Hideo; Natsume, Tohru; Berninghausen, Otto; Matsuo, Yoshitaka; Becker, Thomas; Beckmann, Roland; Inada, Toshifumi

doi:10.1016/j.molcel.2022.08.018

Cited by 20 publications

(27 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 39 The ubiquitination of uS3 is initiated by the Mag2-mediated monoubiquitination, followed by K63-linked polyubiquitination by Hel2 or Fap1. 38 , 39 The deletion of SLH1 , which is the core protein of the RQT complex, leads to the reduction of 18 S NRD activity, 39 suggesting the involvement of the RQT complex in 18 S NRD. Furthermore, the deletion of RQT4 , but not CUE3 , partially suppresses the 18 S NRD activity, 39 implying that the wide range searchable ability of Rqt4 might enable the recognition of the K63-linked ubiquitin chain of uS3.…”

Section: Discussionmentioning

confidence: 99%

“…The decoding of the ubiquitination in translating ribosomes is the key event in activating the ubiquitin-mediated pathways of translational control. The diverse ubiquitinations of the ribosome are observed; e.g., the ubiquitination of ribosomal proteins uS10, uS3, eS7, and uL23 are essential to initiate different pathways: the RQC pathway, 9,11,14 the 18 S non-functional rRNA decay (18 S NRD), 38,39 the no-go decay (NGD), 18 and the ribophagy, 40 respectively. However, the decoding mechanism of ribosome ubiquitin-code remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex

2023

Self Cite

View full text Add to dashboard Cite

The collision sensor Hel2 specifically recognizes colliding ribosomes and ubiquitinates the ribosomal protein uS10, leading to noncanonical subunit dissociation by the ribosome-associated quality control trigger (RQT) complex. Although uS10 ubiquitination is essential for rescuing stalled ribosomes, its function and recognition steps are not fully understood. Here, we show that the RQT complex components Cue3 and Rqt4 interact with the K63-linked ubiquitin chain and accelerate the recruitment of the RQT complex to the ubiquitinated colliding ribosome. The CUE domain of Cue3 and the N-terminal domain of Rqt4 bind independently to the K63-linked ubiquitin chain. Their deletion abolishes ribosomal dissociation mediated by the RQT complex. High-speed atomic force microscopy (HS-AFM) reveals that the intrinsically disordered regions of Rqt4 enable the expansion of the searchable area for interaction with the ubiquitin chain. These findings provide mechanistic insight into the decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex

2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…The decoding of the ubiquitination in translating ribosomes is the key event in activating the ubiquitin-mediated pathways of translational control. The diverse ubiquitinations of the ribosome are observed; e.g., the ubiquitination of ribosomal proteins uS10, uS3, eS7, and uL23 are essential to initiate different pathways: the RQC pathway 9,11,14 , the 18S non-functional rRNA decay (18S NRD) 37,38 , the no-go decay (NGD) 18 , and the ribophagy 39 , respectively. However, the decoding mechanism of ribosome ubiquitin-code remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…The K63-linked ubiquitin chain is also formed on the uS3 and is essential to inducing the 18S NRD pathway 38 . The ubiquitination of uS3 is initiated by the Mag2-mediated monoubiquitination, followed by K63-linked polyubiquitination by Hel2 or Fap1 37,38 . The deletion of SLHJ , which is the core protein of the RQT complex, leads to the reduction of 18S NRD activity 38 , suggesting the involvement of the RQT complex in 18S NRD.…”

Section: Discussionmentioning

confidence: 99%

Decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex

Matsuo

Inada

2022

Preprint

Self Cite

View full text Add to dashboard Cite

The collision sensor Hel2 specifically recognizes colliding ribosomes and ubiquitinates the ribosomal protein uS10, leading to noncanonical subunit dissociation by the ribosome-associated quality control trigger (RQT) complex. Although uS10 ubiquitination is essential for rescuing stalled ribosomes, its function and recognition steps are not fully understood. Here, we showed that the RQT complex components Cue3 and Rqt4 interacted with the K63-linked ubiquitin chain and accelerated the recruitment of the RQT complex to the ubiquitinated colliding ribosome. The CUE domain of Cue3 and the N-terminal domain of Rqt4 bound independently to the K63-linked ubiquitin chain. Their deletion abolished ribosomal dissociation mediated by the RQT complex. The intrinsically disordered regions of Rqt4 enabled the expansion of the searchable area for interaction with the ubiquitin chain. These findings provide mechanistic insight into the decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex.

show abstract

“…Activation of NRD involves polyubiquitination of the 40S protein RPS3 and ribosomal splitting, through a multi-tiered process consisting of mono-ubiquitination and ubiquitin chain elongation by the Mag2 and Fap1 ubiquitin ligases, respectively ( Sugiyama et al, 2019 ). Interestingly, while the NRD-inducing 18S base mutation A1755C led to 80S ribosomes arrested at the initiation codon, selective ribosome profiling experiments showed that both Mag2 and Fap1 prominently associate with ribosomes located within the coding sequence ( Li et al, 2022 ). This observation indicates that NRD decay also targets translating ribosomes, suggesting that defective, truncated nascent proteins might also be produced in the context of NRD-eliciting situations.…”

Section: Emerging Co-translational Quality Control Pathwaysmentioning

confidence: 99%

Ending a bad start: Triggers and mechanisms of co-translational protein degradation

Eisenack

Trentini²

2023

Front. Mol. Biosci.

View full text Add to dashboard Cite

Proteins are versatile molecular machines that control and execute virtually all cellular processes. They are synthesized in a multilayered process requiring transfer of information from DNA to RNA and finally into polypeptide, with many opportunities for error. In addition, nascent proteins must successfully navigate a complex folding-energy landscape, in which their functional native state represents one of many possible outcomes. Consequently, newly synthesized proteins are at increased risk of misfolding and toxic aggregation. To maintain proteostasis–the state of proteome balance–cells employ a plethora of molecular chaperones that guide proteins along a productive folding pathway and quality control factors that direct misfolded species for degradation. Achieving the correct balance between folding and degradation therefore represents a fundamental task for the proteostasis network. While many chaperones act co-translationally, protein quality control is generally considered to be a post-translational process, as the majority of proteins will only achieve their final native state once translation is completed. Nevertheless, it has been observed that proteins can be ubiquitinated during synthesis. The extent and the relevance of co-translational protein degradation, as well as the underlying molecular mechanisms, remain areas of open investigation. Recent studies made seminal advances in elucidating ribosome-associated quality control processes, and how their loss of function can lead to proteostasis failure and disease. Here, we discuss current understanding of the situations leading to the marking of nascent proteins for degradation before synthesis is completed, and the emerging quality controls pathways engaged in this task in eukaryotic cells. We also highlight the methods used to study co-translational quality control.

show abstract

Sensing of individual stalled 80S ribosomes by Fap1 for nonfunctional rRNA turnover

Cited by 20 publications

References 69 publications

Decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex

Decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex

Decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex

Ending a bad start: Triggers and mechanisms of co-translational protein degradation

Contact Info

Product

Resources

About