id: Q9BRX2 gene_symbol: PELO product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: PELO (Protein pelota homolog, the human ortholog of yeast Dom34) is a cytoplasmic ribosome-rescue factor of the eukaryotic release factor 1 (eRF1) family, Pelota subfamily. Structurally it mimics eRF1 and occupies the ribosomal A site, but it lacks the catalytic GGQ motif and therefore has no peptidyl-tRNA hydrolase (peptide-release) activity. PELO forms the Pelota-HBS1L complex (also called the Dom34-Hbs1 complex) with the translational GTPase HBS1L. This complex recognizes ribosomes that are stalled at the 3' end of an mRNA (truncated, non-stop, or no-go messages), engages the empty mRNA channel, and, after mRNA extraction by the SKI complex, recruits the recycling ATPase ABCE1 to split the stalled 80S ribosome into subunits. PELO thereby initiates the no-go decay (NGD) and non-stop decay (NSD) mRNA surveillance pathways and rescues stalled ribosomes. It is ubiquitously expressed and is also recruited, in a PINK1-regulated manner, to mitochondrially associated ribosomes during mitophagy. existing_annotations: - term: id: GO:0022626 label: cytosolic ribosome evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: PELO acts on the cytosolic 80S ribosome, where it occupies the A site of stalled ribosomes. Phylogenetic transfer agrees with direct cryo-EM evidence. action: ACCEPT reason: PELO's site of action is the cytosolic ribosome; supported by direct structural evidence of PELO bound to stalled ribosomes. supported_by: - reference_id: PMID:27863242 supporting_text: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes - term: id: GO:0072344 label: rescue of stalled cytosolic ribosome evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Rescue of stalled ribosomes is the defining biological role of PELO. The IBA inference is corroborated by multiple direct experimental annotations. action: ACCEPT reason: Core biological process for PELO, supported by conserved function across yeast Dom34, Drosophila pelo and human PELO and by direct mammalian biochemistry. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway - term: id: GO:0170011 label: stalled ribosome sensor activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: PELO senses ribosomes stalled at the 3' end of mRNA by probing the (near-)empty mRNA channel/A site, the molecular function underlying rescue. IBA agrees with direct IDA evidence. action: ACCEPT reason: This is PELO's core molecular function; phylogenetic inference is consistent with direct structural evidence. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: PELO recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel - term: id: GO:1990533 label: Dom34-Hbs1 complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: PELO is one of the two subunits of the Dom34-Hbs1 (Pelota-HBS1L) complex. Phylogenetic assignment matches direct evidence. action: ACCEPT reason: PELO is a defining, conserved component of this complex. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: Component of the Pelota-HBS1L complex, also named Dom34-Hbs1 complex, composed of PELO and HBS1L - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Electronic localization to the cytoplasm, consistent with the documented cytoplasmic site of action; less precise than the cytosolic ribosome annotation. action: KEEP_AS_NON_CORE reason: Correct but generic compartment annotation; the informative localization is the cytosolic ribosome / Dom34-Hbs1 complex. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0070481 label: nuclear-transcribed mRNA catabolic process, non-stop decay evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: PELO/HBS1L mediate non-stop decay by recognizing ribosomes that have read to the 3' end of an mRNA lacking a stop codon. Supported by direct experiment. action: ACCEPT reason: NSD is a genuine PELO process; the InterPro IEA is corroborated by direct evidence in mammalian cells. supported_by: - reference_id: PMID:23667253 supporting_text: The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells - term: id: GO:0070966 label: nuclear-transcribed mRNA catabolic process, no-go decay evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: No-go decay is triggered by PELO recognition of stalled ribosomes. The InterPro IEA duplicates better-supported IDA annotations. action: ACCEPT reason: NGD is a core PELO process, supported by direct experimental annotations. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway - term: id: GO:0071025 label: RNA surveillance evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: General mRNA surveillance term; NGD/NSD are the specific PELO surveillance pathways already captured by more precise terms. action: KEEP_AS_NON_CORE reason: Correct but a parent of the specific no-go/non-stop decay terms; retained as a less-informative general annotation. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20406461 qualifier: enables review: summary: High-throughput IntAct interactions (e.g. EIF3G, HAX1, SRPX). Bare protein binding is uninformative; EIF3G is a plausible translation-related partner but not part of the defined complex. action: KEEP_AS_NON_CORE reason: Records real physical interactions but the generic protein binding term adds nothing to PELO's defined ribosome-rescue function. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: 'O75821: EIF3G' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25277244 qualifier: enables review: summary: IntAct interaction with HSPB1 (P04792). Bare protein binding; isolated chaperone interaction not central to ribosome rescue. action: KEEP_AS_NON_CORE reason: Generic protein binding from a single interaction; uninformative for core function. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: 'P04792: HSPB1' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: Yeast two-hybrid interactome capturing the PELO-HBS1L interaction, the one biologically meaningful partner here. action: KEEP_AS_NON_CORE reason: The bare term is uninformative, but the HBS1L partner is the defining one; the functional consequence (Dom34-Hbs1 complex) is captured by GO:1990533. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: 'Q9Y450: HBS1L' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables review: summary: Interactome screen again capturing PELO-HBS1L. Generic term but relevant partner. action: KEEP_AS_NON_CORE reason: Confirms the HBS1L interaction; bare protein binding term is non-core. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: 'Q9Y450: HBS1L' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: Binary interactome map including HBS1L plus various non-specific partners (DYNLT1, LMO3/4, MEOX2, etc.). Bare protein binding. action: KEEP_AS_NON_CORE reason: Mixed interactor set; only HBS1L is functionally relevant and is already captured by the complex annotation. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: 'Q9Y450: HBS1L' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32814053 qualifier: enables review: summary: Neurodegeneration interactome screen capturing many high-throughput partners (HTT, FLNA, NEFL, BAG3, etc.) unrelated to PELO's defined function. action: KEEP_AS_NON_CORE reason: Large set of isolated high-throughput interactions with no clear link to ribosome rescue; bare protein binding term is uninformative. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: 'P42858: HTT' - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9954730 qualifier: located_in review: summary: Reactome curated cytosolic localization in ribosome-rescue reactions, consistent with PELO's site of action. action: KEEP_AS_NON_CORE reason: Correct localization but generic; the cytosolic ribosome / complex annotations are more informative. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9954919 qualifier: located_in review: summary: Reactome curated cytosolic localization (duplicate context). action: KEEP_AS_NON_CORE reason: Correct but generic localization, redundant with other cytosol annotations. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9955731 qualifier: located_in review: summary: Reactome curated cytosolic localization (duplicate context). action: KEEP_AS_NON_CORE reason: Correct but generic localization, redundant with other cytosol annotations. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0022626 label: cytosolic ribosome evidence_type: IDA original_reference_id: PMID:27863242 qualifier: is_active_in review: summary: Direct cryo-EM evidence places PELO on the stalled cytosolic 80S ribosome. action: ACCEPT reason: Strong direct structural evidence for PELO acting on the cytosolic ribosome. supported_by: - reference_id: PMID:27863242 supporting_text: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes - term: id: GO:0170011 label: stalled ribosome sensor activity evidence_type: IDA original_reference_id: PMID:27863242 qualifier: enables review: summary: Direct structural/biochemical demonstration that PELO senses the stalled-ribosome state via the mRNA channel. Core molecular function. action: ACCEPT reason: Best-supported molecular function for PELO; direct IDA evidence. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: PELO recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel - term: id: GO:0032790 label: ribosome disassembly evidence_type: IDA original_reference_id: PMID:21448132 qualifier: involved_in review: summary: With HBS1L and ABCE1, PELO drives dissociation of 80S ribosomes into subunits, demonstrated by in vitro reconstitution. action: ACCEPT reason: Directly demonstrated; ribosome disassembly (subunit splitting) is the mechanistic output of PELO-mediated rescue. supported_by: - reference_id: PMID:21448132 supporting_text: Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes - term: id: GO:0043022 label: ribosome binding evidence_type: IDA original_reference_id: PMID:27543824 qualifier: enables review: summary: PELO binds the ribosome; the K2A and R45A mutants that abolish rescue map to the ribosome/mRNA-channel-engaging surface. action: ACCEPT reason: Directly demonstrated ribosome binding underlying rescue activity. supported_by: - reference_id: PMID:27543824 supporting_text: Conserved functions of human Pelota in mRNA quality control of nonstop mRNA - term: id: GO:0043022 label: ribosome binding evidence_type: IDA original_reference_id: PMID:27863242 qualifier: enables review: summary: Cryo-EM directly shows PELO bound to the stalled ribosome. action: ACCEPT reason: Direct structural evidence of ribosome binding. supported_by: - reference_id: PMID:27863242 supporting_text: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes - term: id: GO:0070966 label: nuclear-transcribed mRNA catabolic process, no-go decay evidence_type: IDA original_reference_id: PMID:23667253 qualifier: involved_in review: summary: PELO/HBS1L drive no-go/non-stop decay of aberrant mRNAs in mammalian cells. action: ACCEPT reason: Directly demonstrated NGD role. supported_by: - reference_id: PMID:23667253 supporting_text: The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells - term: id: GO:0070966 label: nuclear-transcribed mRNA catabolic process, no-go decay evidence_type: IDA original_reference_id: PMID:27543824 qualifier: involved_in review: summary: Human Pelota functions in mRNA quality control of nonstop mRNA; loss-of-function mutants abolish activity. action: ACCEPT reason: Direct mutagenesis-supported evidence for PELO in no-go/non-stop mRNA decay. supported_by: - reference_id: PMID:27543824 supporting_text: Conserved functions of human Pelota in mRNA quality control of nonstop mRNA - term: id: GO:0070966 label: nuclear-transcribed mRNA catabolic process, no-go decay evidence_type: IDA original_reference_id: PMID:27863242 qualifier: involved_in review: summary: Structural study supporting PELO's role in recognizing stalled ribosomes that triggers no-go decay. action: ACCEPT reason: Direct evidence for the NGD-triggering recognition step. supported_by: - reference_id: PMID:27863242 supporting_text: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes - term: id: GO:0072344 label: rescue of stalled cytosolic ribosome evidence_type: IDA original_reference_id: PMID:21448132 qualifier: involved_in review: summary: In vitro reconstitution shows PELO (with HBS1L/ABCE1) rescues stalled elongation complexes. Core process. action: ACCEPT reason: Directly demonstrated core biological process of PELO. supported_by: - reference_id: PMID:21448132 supporting_text: Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes - term: id: GO:0072344 label: rescue of stalled cytosolic ribosome evidence_type: IDA original_reference_id: PMID:27863242 qualifier: involved_in review: summary: Structural demonstration of PELO engaging stalled ribosomes for rescue. action: ACCEPT reason: Direct structural evidence for the core rescue process. supported_by: - reference_id: PMID:27863242 supporting_text: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes - term: id: GO:1990533 label: Dom34-Hbs1 complex evidence_type: IDA original_reference_id: PMID:27863242 qualifier: part_of review: summary: PELO directly identified as a component of the Pelota-HBS1L (Dom34-Hbs1) complex by cryo-EM. action: ACCEPT reason: Direct evidence for PELO as a complex subunit. supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: Component of the Pelota-HBS1L complex, also named Dom34-Hbs1 complex, composed of PELO and HBS1L references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping findings: [] - id: PMID:20406461 title: Pelota interacts with HAX1, EIF3G and SRPX and the resulting protein complexes are associated with the actin cytoskeleton. findings: [] - id: PMID:21448132 title: Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes. findings: - statement: Pelota, Hbs1 and ABCE1 together dissociate vacant 80S ribosomes and stalled elongation complexes into subunits. reference_section_type: RESULTS reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached publication title matches; establishes the PELO-HBS1L-ABCE1 ribosome dissociation/recycling activity (anchors GO:0043022 ribosome binding IDA in GOA). - id: PMID:23667253 title: The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells. findings: - statement: The mammalian Hbs1-Dom34 (HBS1L-PELO) complex functions in non-stop mRNA decay. reference_section_type: RESULTS reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached publication title matches; establishes PELO-HBS1L role in non-stop mRNA decay (GO:0070966). - id: PMID:25277244 title: The functional landscape of Hsp27 reveals new cellular processes such as DNA repair and alternative splicing and proposes novel anticancer targets. findings: [] - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:27543824 title: Conserved functions of human Pelota in mRNA quality control of nonstop mRNA. findings: - statement: Human Pelota functions in mRNA quality control of nonstop mRNA; the K2A and R45A mutants abolish its ability to rescue stalled ribosomes. reference_section_type: RESULTS reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached publication title matches; mutational analysis establishes human PELO's stalled-ribosome rescue function in nonstop mRNA QC. - id: PMID:27863242 title: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes. findings: - statement: Cryo-EM of the PELO-HBS1L complex on stalled ribosomes defines PELO's stalled-ribosome sensor activity and ribosome binding. reference_section_type: RESULTS reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached publication title matches; cryo-EM structural evidence supports the stalled-ribosome sensor activity (GO:0170011 IDA in GOA). - id: PMID:31515488 title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:32814053 title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. findings: [] - id: Reactome:R-HSA-9954730 title: Reactome ribosome quality control reaction (PELO cytosol) findings: [] - id: Reactome:R-HSA-9954919 title: Reactome ribosome quality control reaction (PELO cytosol) findings: [] - id: Reactome:R-HSA-9955731 title: Reactome ribosome quality control reaction (PELO cytosol) findings: [] core_functions: - description: Stalled-ribosome sensor / eRF1-like factor that recognizes ribosomes stalled at the 3' end of an mRNA by probing the empty mRNA channel and A site, the molecular recognition event that initiates ribosome rescue. Unlike eRF1, PELO lacks peptidyl-tRNA hydrolase activity. molecular_function: id: GO:0170011 label: stalled ribosome sensor activity locations: - id: GO:0022626 label: cytosolic ribosome supported_by: - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: PELO recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel - description: As the eRF1-like subunit of the Pelota-HBS1L (Dom34-Hbs1) complex, with the GTPase HBS1L and recycling ATPase ABCE1, PELO rescues stalled ribosomes by driving their dissociation into subunits, initiating no-go and non-stop mRNA decay. molecular_function: id: GO:0043022 label: ribosome binding in_complex: id: GO:1990533 label: Dom34-Hbs1 complex supported_by: - reference_id: PMID:21448132 supporting_text: Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes - reference_id: file:human/PELO/PELO-uniprot.txt supporting_text: Component of the Pelota-HBS1L complex, also named Dom34-Hbs1 complex, composed of PELO and HBS1L proposed_new_terms: [] suggested_questions: - question: How is the choice between productive translation termination (eRF1) and rescue (PELO) made at ribosomes with short or empty mRNA in the channel? - question: What is the in vivo contribution of the PINK1-regulated PELO recruitment to mitochondrial ribosomes relative to its canonical cytosolic rescue role? suggested_experiments: - description: Ribosome profiling and 5'P degradome sequencing in PELO-knockout versus wild-type human cells to quantify accumulation of stalled/truncated mRNAs and define the endogenous no-go/non-stop substrate repertoire. - description: Reconstituted single-molecule or cryo-EM time-resolved analysis of PELO-HBS1L-ABCE1 splitting kinetics on defined stalled substrates to dissect the mRNA-channel sensing step.