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
|
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.
UniProt: Q9BRX2. Member of the eukaryotic release factor 1 (eRF1) family, Pelota subfamily. 385 aa, cytoplasmic.
PELO is the eRF1-like component of the Pelota-HBS1L (Dom34-Hbs1) complex, a ribosome-rescue
machine. Unlike eRF1, it has no peptidyl-tRNA hydrolase (peptide release) activity; it instead
recognizes ribosomes stalled at the 3' end of an mRNA (truncated/non-stop, no-go) and, together
with the GTPase HBS1L and the recycling ATPase ABCE1, drives subunit dissociation (ribosome
disassembly), initiating No-Go Decay (NGD) and Non-Stop Decay (NSD).
protein binding IPI rows are high-throughput interactors (HSPB1, HTT, FLNA, etc.); HBS1L (Q9Y450) and EIF3G/ABCE1 are the biologically meaningful ones. Bare GO:0005515 is uninformative.*-deep-research*.md file found in this gene directory.Translation|Cytosolic translation|Ribosome-associated QC|Ribosomal rescue. PN-node mapping: rescue-typeβmapped GO:0072344 rescue of stalled cytosolic ribosome (already_in_goa_exact); RQC-groupβmapped GO:0006515 protein QC (new_to_goa); class/branch context_only. Projected: GO:0072344 (already in GOA), GO:0006515 (new).This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.
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.