Translation initiation complex formation / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Formation of a pool of free 40S subunits / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Major pathway of rRNA processing in the nucleolus and cytosol ...Translation initiation complex formation / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Formation of a pool of free 40S subunits / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Major pathway of rRNA processing in the nucleolus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / Formation of a pool of free 40S subunits / SRP-dependent cotranslational protein targeting to membrane / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Translation initiation complex formation / Ribosomal scanning and start codon recognition / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / translation at presynapse / male meiosis I / negative regulation of protein neddylation / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of formation of translation preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of endodeoxyribonuclease activity / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / supercoiled DNA binding / TORC2 complex binding / alpha-beta T cell differentiation / neural crest cell differentiation / NF-kappaB complex / positive regulation of ubiquitin-protein transferase activity / oxidized purine DNA binding / ubiquitin-like protein conjugating enzyme binding / negative regulation of bicellular tight junction assembly / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / Ribosomal scanning and start codon recognition / homeostatic process / Translation initiation complex formation / organelle membrane / positive regulation of T cell receptor signaling pathway / macrophage chemotaxis / fibroblast growth factor binding / lung morphogenesis / positive regulation of activated T cell proliferation / positive regulation of natural killer cell proliferation / Protein hydroxylation / TOR signaling / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / cellular response to ethanol / iron-sulfur cluster binding / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / negative regulation of ubiquitin-dependent protein catabolic process / positive regulation of signal transduction by p53 class mediator / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / protein localization to nucleus / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / positive regulation of protein binding / protein targeting / Major pathway of rRNA processing in the nucleolus and cytosol / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / protein-RNA complex assembly / Protein methylation / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / maturation of LSU-rRNA / spindle assembly / Nuclear events stimulated by ALK signaling in cancer / rough endoplasmic reticulum / laminin binding / translation regulator activity / positive regulation of cell cycle / translation initiation factor binding / gastrulation / positive regulation of microtubule polymerization / DNA-(apurinic or apyrimidinic site) endonuclease activity / MDM2/MDM4 family protein binding Similarity search - Function
40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / Ribosomal protein L30e / Ribosomal protein L28e ...40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / Ribosomal protein L30e / Ribosomal protein L28e / Ribosomal L15/L27a, N-terminal / Ribosomal protein L13e / Ribosomal protein L2, archaeal-type / Ribosomal protein L23 / Ribosomal protein L30e signature 1. / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / Ribosomal protein L30e signature 2. / Ribosomal protein L30e, conserved site / Ribosomal protein L13e / Ribosomal protein L30/YlxQ / metallochaperone-like domain / TRASH domain / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / : / Ribosomal protein S12e signature. / Ribosomal protein S12e / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Ribosomal protein S5, eukaryotic/archaeal / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S2, eukaryotic / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / S27a-like superfamily / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / Ribosomal protein L10e / 40S Ribosomal protein S10 / : / Ribosomal protein L44e signature. / Ribosomal protein S7e signature. / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19, eukaryotic / Ribosomal protein L19e signature. / Plectin/S10, N-terminal / Plectin/S10 domain / : / 60S ribosomal protein L18a/ L20, eukaryotes / Ribosomal protein L6e signature. / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein S8e subdomain, eukaryotes / : / Ribosomal protein S17e, conserved site / Ribosomal protein S17e signature. / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein L44e / Ribosomal protein S3Ae, conserved site / Ribosomal protein L44 / Ribosomal protein S3Ae signature. / Ribosomal protein S30 / Ribosomal protein S30 / Ribosomal protein S27a / Ribosomal protein L34e, conserved site / Ribosomal protein S27a / Ribosomal protein L34e signature. / Ribosomal protein S27a / Ribosomal protein S2, eukaryotic/archaeal / Ribosomal protein L5 eukaryotic, C-terminal / 50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a / Ribosomal L18 C-terminal region / Ribosomal L40e family / Ribosomal protein 50S-L18Ae/60S-L20/60S-L18A / Ribosomal proteins 50S-L18Ae/60S-L20/60S-L18A / Ribosomal protein 60S L18 and 50S L18e / Ribosomal_L40e / Ribosomal protein L40e / Ribosomal protein L40e superfamily Similarity search - Domain/homology
Large ribosomal subunit protein eL38 / Large ribosomal subunit protein eL34 / Ribosomal protein L19 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein RACK1 / 40S ribosomal protein S15 / Ubiquitin-like domain-containing protein / Small ribosomal subunit protein eS19 / Ribosomal protein L37 ...Large ribosomal subunit protein eL38 / Large ribosomal subunit protein eL34 / Ribosomal protein L19 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein RACK1 / 40S ribosomal protein S15 / Ubiquitin-like domain-containing protein / Small ribosomal subunit protein eS19 / Ribosomal protein L37 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein eS28 / Large ribosomal subunit protein uL14 / Small ribosomal subunit protein uS9 / KOW domain-containing protein / Small ribosomal subunit protein uS15 / 40S ribosomal protein S12 / Large ribosomal subunit protein eL43 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 / 40S ribosomal protein S26 / 40S ribosomal protein S25 / 40S ribosomal protein S27 / Small ribosomal subunit protein uS11 / Large ribosomal subunit protein eL39 / 60S ribosomal protein L27 / Large ribosomal subunit protein uL2 / Small ribosomal subunit protein uS17 / Ubiquitin-ribosomal protein eS31 fusion protein / Ubiquitin-ribosomal protein eL40 fusion protein / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL31 / Small ribosomal subunit protein uS13 / Ribosomal protein L36a / Ribosomal protein L15 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Small ribosomal subunit protein uS3 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL13 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein eL28 / Small ribosomal subunit protein eS10 / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL14 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein eS1 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Large ribosomal subunit protein eL8 / Small ribosomal subunit protein eS4, X isoform / Large ribosomal subunit protein uL23 / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein eS24 / Large ribosomal subunit protein eL30 / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL5 / Small ribosomal subunit protein eS32 / Small ribosomal subunit protein eS21 / Large ribosomal subunit protein eL20 / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein eL18 / Ribosomal protein uL16-like / Large ribosomal subunit protein eL36 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 3.0 Å
Journal: Nat Commun / Year: 2022 Title: A distinct mammalian disome collision interface harbors K63-linked polyubiquitination of uS10 to trigger hRQT-mediated subunit dissociation. Authors: Momoko Narita / Timo Denk / Yoshitaka Matsuo / Takato Sugiyama / Chisato Kikuguchi / Sota Ito / Nichika Sato / Toru Suzuki / Satoshi Hashimoto / Iva Machová / Petr Tesina / Roland Beckmann ...Authors: Momoko Narita / Timo Denk / Yoshitaka Matsuo / Takato Sugiyama / Chisato Kikuguchi / Sota Ito / Nichika Sato / Toru Suzuki / Satoshi Hashimoto / Iva Machová / Petr Tesina / Roland Beckmann / Toshifumi Inada / Abstract: Translational stalling events that result in ribosome collisions induce Ribosome-associated Quality Control (RQC) in order to degrade potentially toxic truncated nascent proteins. For RQC induction, ...Translational stalling events that result in ribosome collisions induce Ribosome-associated Quality Control (RQC) in order to degrade potentially toxic truncated nascent proteins. For RQC induction, the collided ribosomes are first marked by the Hel2/ZNF598 E3 ubiquitin ligase to recruit the RQT complex for subunit dissociation. In yeast, uS10 is polyubiquitinated by Hel2, whereas eS10 is preferentially monoubiquitinated by ZNF598 in human cells for an unknown reason. Here, we characterize the ubiquitination activity of ZNF598 and its importance for human RQT-mediated subunit dissociation using the endogenous XBP1u and poly(A) translation stallers. Cryo-EM analysis of a human collided disome reveals a distinct composite interface, with substantial differences to yeast collided disomes. Biochemical analysis of collided ribosomes shows that ZNF598 forms K63-linked polyubiquitin chains on uS10, which are decisive for mammalian RQC initiation. The human RQT (hRQT) complex composed only of ASCC3, ASCC2 and TRIP4 dissociates collided ribosomes dependent on the ATPase activity of ASCC3 and the ubiquitin-binding capacity of ASCC2. The hRQT-mediated subunit dissociation requires the K63-linked polyubiquitination of uS10, while monoubiquitination of eS10 or uS10 is not sufficient. Therefore, we conclude that ZNF598 functionally marks collided mammalian ribosomes by K63-linked polyubiquitination of uS10 for the trimeric hRQT complex-mediated subunit dissociation.
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