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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0022626 cytosolic ribosome | IBA GO_REF:0000033 | ACCEPT | 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. Reason: PELO's site of action is the cytosolic ribosome; supported by direct structural evidence of PELO bound to stalled ribosomes. Supporting Evidence: PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes |
| GO:0072344 rescue of stalled cytosolic ribosome | IBA GO_REF:0000033 | ACCEPT | Summary: Rescue of stalled ribosomes is the defining biological role of PELO. The IBA inference is corroborated by multiple direct experimental annotations. Reason: Core biological process for PELO, supported by conserved function across yeast Dom34, Drosophila pelo and human PELO and by direct mammalian biochemistry. Supporting Evidence: file:human/PELO/PELO-uniprot.txt a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway |
| GO:0170011 stalled ribosome sensor activity | IBA GO_REF:0000033 | ACCEPT | 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. Reason: This is PELO's core molecular function; phylogenetic inference is consistent with direct structural evidence. Supporting Evidence: file:human/PELO/PELO-uniprot.txt PELO recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel |
| GO:1990533 Dom34-Hbs1 complex | IBA GO_REF:0000033 | ACCEPT | Summary: PELO is one of the two subunits of the Dom34-Hbs1 (Pelota-HBS1L) complex. Phylogenetic assignment matches direct evidence. Reason: PELO is a defining, conserved component of this complex. Supporting Evidence: file:human/PELO/PELO-uniprot.txt Component of the Pelota-HBS1L complex, also named Dom34-Hbs1 complex, composed of PELO and HBS1L |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic localization to the cytoplasm, consistent with the documented cytoplasmic site of action; less precise than the cytosolic ribosome annotation. Reason: Correct but generic compartment annotation; the informative localization is the cytosolic ribosome / Dom34-Hbs1 complex. Supporting Evidence: file:human/PELO/PELO-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0070481 nuclear-transcribed mRNA catabolic process, non-stop decay | IEA GO_REF:0000002 | ACCEPT | 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. Reason: NSD is a genuine PELO process; the InterPro IEA is corroborated by direct evidence in mammalian cells. Supporting Evidence: PMID:23667253 The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells |
| GO:0070966 nuclear-transcribed mRNA catabolic process, no-go decay | IEA GO_REF:0000002 | ACCEPT | Summary: No-go decay is triggered by PELO recognition of stalled ribosomes. The InterPro IEA duplicates better-supported IDA annotations. Reason: NGD is a core PELO process, supported by direct experimental annotations. Supporting Evidence: file:human/PELO/PELO-uniprot.txt a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway |
| GO:0071025 RNA surveillance | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: General mRNA surveillance term; NGD/NSD are the specific PELO surveillance pathways already captured by more precise terms. Reason: Correct but a parent of the specific no-go/non-stop decay terms; retained as a less-informative general annotation. Supporting Evidence: file:human/PELO/PELO-uniprot.txt a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway |
| GO:0005515 protein binding | IPI PMID:20406461 Pelota interacts with HAX1, EIF3G and SRPX and the resulting... | KEEP AS NON CORE | 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. Reason: Records real physical interactions but the generic protein binding term adds nothing to PELO's defined ribosome-rescue function. Supporting Evidence: file:human/PELO/PELO-uniprot.txt O75821: EIF3G |
| GO:0005515 protein binding | IPI PMID:25277244 The functional landscape of Hsp27 reveals new cellular proce... | KEEP AS NON CORE | Summary: IntAct interaction with HSPB1 (P04792). Bare protein binding; isolated chaperone interaction not central to ribosome rescue. Reason: Generic protein binding from a single interaction; uninformative for core function. Supporting Evidence: file:human/PELO/PELO-uniprot.txt P04792: HSPB1 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Yeast two-hybrid interactome capturing the PELO-HBS1L interaction, the one biologically meaningful partner here. 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. Supporting Evidence: file:human/PELO/PELO-uniprot.txt Q9Y450: HBS1L |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Interactome screen again capturing PELO-HBS1L. Generic term but relevant partner. Reason: Confirms the HBS1L interaction; bare protein binding term is non-core. Supporting Evidence: file:human/PELO/PELO-uniprot.txt Q9Y450: HBS1L |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary interactome map including HBS1L plus various non-specific partners (DYNLT1, LMO3/4, MEOX2, etc.). Bare protein binding. Reason: Mixed interactor set; only HBS1L is functionally relevant and is already captured by the complex annotation. Supporting Evidence: file:human/PELO/PELO-uniprot.txt Q9Y450: HBS1L |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Neurodegeneration interactome screen capturing many high-throughput partners (HTT, FLNA, NEFL, BAG3, etc.) unrelated to PELO's defined function. Reason: Large set of isolated high-throughput interactions with no clear link to ribosome rescue; bare protein binding term is uninformative. Supporting Evidence: file:human/PELO/PELO-uniprot.txt P42858: HTT |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9954730 | KEEP AS NON CORE | Summary: Reactome curated cytosolic localization in ribosome-rescue reactions, consistent with PELO's site of action. Reason: Correct localization but generic; the cytosolic ribosome / complex annotations are more informative. Supporting Evidence: file:human/PELO/PELO-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9954919 | KEEP AS NON CORE | Summary: Reactome curated cytosolic localization (duplicate context). Reason: Correct but generic localization, redundant with other cytosol annotations. Supporting Evidence: file:human/PELO/PELO-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9955731 | KEEP AS NON CORE | Summary: Reactome curated cytosolic localization (duplicate context). Reason: Correct but generic localization, redundant with other cytosol annotations. Supporting Evidence: file:human/PELO/PELO-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0022626 cytosolic ribosome | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: Direct cryo-EM evidence places PELO on the stalled cytosolic 80S ribosome. Reason: Strong direct structural evidence for PELO acting on the cytosolic ribosome. Supporting Evidence: PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes |
| GO:0170011 stalled ribosome sensor activity | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: Direct structural/biochemical demonstration that PELO senses the stalled-ribosome state via the mRNA channel. Core molecular function. Reason: Best-supported molecular function for PELO; direct IDA evidence. Supporting Evidence: file:human/PELO/PELO-uniprot.txt PELO recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel |
| GO:0032790 ribosome disassembly | IDA PMID:21448132 Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 8... | ACCEPT | Summary: With HBS1L and ABCE1, PELO drives dissociation of 80S ribosomes into subunits, demonstrated by in vitro reconstitution. Reason: Directly demonstrated; ribosome disassembly (subunit splitting) is the mechanistic output of PELO-mediated rescue. Supporting Evidence: PMID:21448132 Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes |
| GO:0043022 ribosome binding | IDA PMID:27543824 Conserved functions of human Pelota in mRNA quality control ... | ACCEPT | Summary: PELO binds the ribosome; the K2A and R45A mutants that abolish rescue map to the ribosome/mRNA-channel-engaging surface. Reason: Directly demonstrated ribosome binding underlying rescue activity. Supporting Evidence: PMID:27543824 Conserved functions of human Pelota in mRNA quality control of nonstop mRNA |
| GO:0043022 ribosome binding | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: Cryo-EM directly shows PELO bound to the stalled ribosome. Reason: Direct structural evidence of ribosome binding. Supporting Evidence: PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes |
| GO:0070966 nuclear-transcribed mRNA catabolic process, no-go decay | IDA PMID:23667253 The Hbs1-Dom34 protein complex functions in non-stop mRNA de... | ACCEPT | Summary: PELO/HBS1L drive no-go/non-stop decay of aberrant mRNAs in mammalian cells. Reason: Directly demonstrated NGD role. Supporting Evidence: PMID:23667253 The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells |
| GO:0070966 nuclear-transcribed mRNA catabolic process, no-go decay | IDA PMID:27543824 Conserved functions of human Pelota in mRNA quality control ... | ACCEPT | Summary: Human Pelota functions in mRNA quality control of nonstop mRNA; loss-of-function mutants abolish activity. Reason: Direct mutagenesis-supported evidence for PELO in no-go/non-stop mRNA decay. Supporting Evidence: PMID:27543824 Conserved functions of human Pelota in mRNA quality control of nonstop mRNA |
| GO:0070966 nuclear-transcribed mRNA catabolic process, no-go decay | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: Structural study supporting PELO's role in recognizing stalled ribosomes that triggers no-go decay. Reason: Direct evidence for the NGD-triggering recognition step. Supporting Evidence: PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:21448132 Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 8... | ACCEPT | Summary: In vitro reconstitution shows PELO (with HBS1L/ABCE1) rescues stalled elongation complexes. Core process. Reason: Directly demonstrated core biological process of PELO. Supporting Evidence: PMID:21448132 Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: Structural demonstration of PELO engaging stalled ribosomes for rescue. Reason: Direct structural evidence for the core rescue process. Supporting Evidence: PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes |
| GO:1990533 Dom34-Hbs1 complex | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: PELO directly identified as a component of the Pelota-HBS1L (Dom34-Hbs1) complex by cryo-EM. Reason: Direct evidence for PELO as a complex subunit. Supporting Evidence: file:human/PELO/PELO-uniprot.txt Component of the Pelota-HBS1L complex, also named Dom34-Hbs1 complex, composed of PELO and HBS1L |
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Download this section (compressed HTML)Q: How is the choice between productive translation termination (eRF1) and rescue (PELO) made at ribosomes with short or empty mRNA in the channel?
Q: What is the in vivo contribution of the PINK1-regulated PELO recruitment to mitochondrial ribosomes relative to its canonical cytosolic rescue role?
Experiment: 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.
Experiment: 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.
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