Details for: PELO

Gene ID: 53918

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PELO

Ensembl ID: ENSG00000152684

Description: pelota mRNA surveillance and ribosome rescue factor

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • secretory cell CL0000151
    CSI 11.91
    rCSI 12.43%
    PRS 89.34
  • progenitor cell CL0011026
    CSI 8.53
    rCSI 18.14%
    PRS 84.76
  • basal-myoepithelial cell of mammary gland CL0002324
    CSI 8.23
    rCSI 15.56%
    PRS 95.4
  • perivascular cell CL4033054
    CSI 5.91
    rCSI 8.08%
    PRS 93.33
  • blood vessel endothelial cell CL0000071
    CSI 4.57
    rCSI 9.48%
    PRS 88.82
  • bronchus fibroblast of lung CL2000093
    CSI 4.34
    rCSI 3.53%
    PRS 89.7
  • vascular associated smooth muscle cell CL0000359
    CSI 3.91
    rCSI 12.69%
    PRS 88.63
  • lung pericyte CL0009089
    CSI 3.49
    rCSI 9.22%
    PRS 94.12
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.24
    rCSI 3.55%
    PRS 91.86
  • CD4-positive helper T cell CL0000492
    CSI 3.21
    rCSI 2.43%
    PRS 96.75
  • fibroblast of lung CL0002553
    CSI 3.2
    rCSI 2.98%
    PRS 91.63
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 3.13
    rCSI 4.89%
    PRS 96.79
  • rod bipolar cell CL0000751
    CSI 3.06
    rCSI 5.49%
    PRS 85.49
  • pulmonary capillary endothelial cell CL4028001
    CSI 3.05
    rCSI 5.82%
    PRS 95.5
  • extravillous trophoblast CL0008036
    CSI 2.98
    rCSI 3.69%
    PRS 88.95
  • myofibroblast cell CL0000186
    CSI 2.94
    rCSI 4.06%
    PRS 87.22
  • neural crest cell CL0011012
    CSI 2.9
    rCSI 2.29%
    PRS 83.57
  • placental villous trophoblast CL2000060
    CSI 2.87
    rCSI 4.43%
    PRS 88.78
  • epithelial cell of lung CL0000082
    CSI 2.81
    rCSI 2.33%
    PRS 91.22
  • group 3 innate lymphoid cell CL0001071
    CSI 2.79
    rCSI 2.09%
    PRS 93.58
  • ciliated epithelial cell CL0000067
    CSI 2.77
    rCSI 2.43%
    PRS 82.02
  • enteric smooth muscle cell CL0002504
    CSI 2.72
    rCSI 3.88%
    PRS 90.51
  • interstitial cell of Cajal CL0002088
    CSI 2.72
    rCSI 3.46%
    PRS 93.79
  • mesodermal cell CL0000222
    CSI 2.67
    rCSI 3.2%
    PRS 89.23
  • cerebral cortex endothelial cell CL1001602
    CSI 2.65
    rCSI 4.58%
    PRS 85.16
  • tracheobronchial smooth muscle cell CL0019019
    CSI 2.64
    rCSI 4.66%
    PRS 92.98
  • pancreatic stellate cell CL0002410
    CSI 2.49
    rCSI 14.47%
    PRS 91.84
  • intestine goblet cell CL0019031
    CSI 2.28
    rCSI 2.03%
    PRS 88
  • stem cell CL0000034
    CSI 2.22
    rCSI 2.14%
    PRS 86.39
  • lung ciliated cell CL1000271
    CSI 2.15
    rCSI 2.49%
    PRS 85.04
  • peripheral nervous system neuron CL2000032
    CSI 2.15
    rCSI 2.93%
    PRS 84.17
  • myeloid leukocyte CL0000766
    CSI 2.14
    rCSI 1.98%
    PRS 91.54
  • microcirculation associated smooth muscle cell CL0008035
    CSI 2.14
    rCSI 6.2%
    PRS 89.52
  • memory T cell CL0000813
    CSI 2.1
    rCSI 4.05%
    PRS 97.87
  • retinal blood vessel endothelial cell CL0002585
    CSI 1.94
    rCSI 3.1%
    PRS 92.61
  • club cell CL0000158
    CSI 1.8
    rCSI 2.64%
    PRS 86.03
  • T-helper 1 cell CL0000545
    CSI 1.7
    rCSI 3.06%
    PRS 96.79
  • endothelial cell of vascular tree CL0002139
    CSI 1.68
    rCSI 9.16%
    PRS 86.64
  • pulmonary artery endothelial cell CL1001568
    CSI 1.66
    rCSI 2.25%
    PRS 94.62
  • basal cell CL0000646
    CSI 1.6
    rCSI 2.13%
    PRS 87.8
  • retinal cone cell CL0000573
    CSI 1.51
    rCSI 2.43%
    PRS 82.81
  • pancreatic acinar cell CL0002064
    CSI 1.5
    rCSI 1.99%
    PRS 93.2
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.42
    rCSI 2.82%
    PRS 96.58
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.38
    rCSI 2.44%
    PRS 77.06
  • pancreatic ductal cell CL0002079
    CSI 1.32
    rCSI 2.57%
    PRS 91.96
  • type B pancreatic cell CL0000169
    CSI 1.28
    rCSI 2.83%
    PRS 90.39
  • mesenchymal cell CL0008019
    CSI 1.09
    rCSI 2.76%
    PRS 85.31
  • prostate gland microvascular endothelial cell CL2000059
    CSI 0.33
    rCSI 7.92%
    PRS 93.51
  • blood vessel smooth muscle cell CL0019018
    CSI 0.32
    rCSI 2.63%
    PRS 87.7

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PELO](/details-gene/53918) (Pelota) is a protein-coding gene located on chromosome 5q11.2 that encodes a highly conserved factor essential for mRNA surveillance and ribosome rescue. Functionally, [PELO](/details-gene/53918) acts as a sensor for stalled ribosomes, forming a complex with HBS1 and ABCE1 to dissociate ribosomal subunits from problematic mRNA transcripts, thereby preventing the accumulation of aberrant proteins and recycling ribosomes for new rounds of translation ([Link](https://pubmed.ncbi.nlm.nih.gov/21448132/)). This quality control mechanism is critical for maintaining proteostasis. **Overall**, expression data highlights its particular significance in cells with high metabolic and proliferative activity, such as [secretory cell](/details-cell/CL0000151) and [progenitor cell](/details-cell/CL0011026), suggesting a fundamental role in supporting cellular processes that demand high rates of protein synthesis and cell division. ## Cellular Roles and Expression Landscape The expression profile of [PELO](/details-gene/53918) underscores its role as a key housekeeping gene with heightened importance in specific cellular contexts. **Overall**, its highest significance is observed in cells characterized by high protein synthesis and export, as evidenced by its top rank in [secretory cell](/details-cell/CL0000151) (CSI: 11.91) and [basal-myoepithelial cell of mammary gland](/details-cell/CL0002324) (CSI: 8.23). This is consistent with its established function in ribosome rescue, a process that is vital for cells managing a large translational load. Furthermore, [PELO](/details-gene/53918) shows significant expression in various progenitor and developing cell populations, including [progenitor cell](/details-cell/CL0011026) (CSI: 8.53), [extravillous trophoblast](/details-cell/CL0008036) (CSI: 2.98), and developing lymphocytes like [CD8-positive, alpha-beta thymocyte](/details-cell/CL0000811) (CSI: 3.13). This pattern aligns with its annotated roles in cell division and stem cell maintenance, indicating that rapidly dividing cells rely heavily on [PELO](/details-gene/53918) to ensure translational fidelity during proliferation. The gene also demonstrates moderate but significant expression across a wide range of stromal and vascular cells, including [perivascular cell](/details-cell/CL4033054), [blood vessel endothelial cell](/details-cell/CL0000071), and various fibroblasts. This broad expression suggests a universal requirement for its mRNA surveillance functions across diverse tissues to maintain basic cellular health and function. ## Pathways and Molecular Function The molecular functions of [PELO](/details-gene/53918) are centered on maintaining the integrity of the cell's translation machinery. It is a core component of several critical RNA quality control pathways, including '[Rna surveillance](/details-cell/GO:0071025)', '[Nuclear-transcribed mrna catabolic process, no-go decay](/details-cell/GO:0070966)', and '[Nuclear-transcribed mrna catabolic process, non-stop decay](/details-cell/GO:0070481)' ([Link](https://pubmed.ncbi.nlm.nih.gov/23667253/)). As a key '[Stalled ribosome sensor activity](/details-cell/GO:0170011)', [PELO](/details-gene/53918) binds to vacant A-sites in ribosomes, initiating the '[Rescue of stalled ribosome](/details-cell/GO:0072344)' and subsequent '[Ribosome disassembly](/details-cell/GO:0032790)'. This role is mediated through its participation in the '[Dom34-hbs1 complex](/details-cell/GO:1990533)', which is essential for resolving translation stalls ([Link](https://pubmed.ncbi.nlm.nih.gov/21448132/)). Consistent with its high expression in progenitor and developing cells, [PELO](/details-gene/53918) is also implicated in fundamental developmental processes. Gene Ontology annotations link it to '[Cell division](/details-cell/GO:0051301)', '[Inner cell mass cell proliferation](/details-cell/GO:0001833)', and '[Stem cell population maintenance](/details-cell/GO:0019827)'. Its involvement in these pathways highlights its necessity for cellular proliferation and the proper execution of developmental programs, where precise control of protein synthesis is paramount. ## Research Directions The widespread and fundamental role of [PELO](/details-gene/53918) in protein quality control makes it a critical gene for cellular health. Future research should focus on its role in pathologies associated with high metabolic stress and abnormal proliferation, such as cancer and neurodegenerative diseases involving protein aggregation. **Testable Hypotheses:** 1. Given its role in maintaining stem cell populations, conditional knockout of [PELO](/details-gene/53918) in adult stem cell niches (e.g., intestinal crypts or hematopoietic stem cells) will lead to premature depletion of the stem cell pool and impaired tissue regeneration due to an accumulation of translational errors and subsequent cell stress. 2. Cancer cells, particularly those with high rates of proliferation and aneuploidy, exhibit increased translational stress and are therefore hypersensitive to the partial inhibition of [PELO](/details-gene/53918). Reducing [PELO](/details-gene/53918) function may represent a synthetic lethal strategy in combination with other agents that disrupt proteostasis. **Proposed Experiment:** To test the second hypothesis, one could utilize a panel of cancer cell lines with varying proliferation rates. [PELO](/details-gene/53918) expression could be knocked down using a doxycycline-inducible shRNA system. The effect of [PELO](/details-gene/53918) knockdown on cell viability and proliferation could be measured alone and in combination with a proteasome inhibitor (e.g., bortezomib). A synergistic reduction in cell viability in the combination treatment group, particularly in rapidly dividing cell lines, would support the hypothesis that cancer cells are uniquely vulnerable to disruptions in ribosome rescue pathways. Readouts would include cell viability assays (e.g., CellTiter-Glo), apoptosis markers (cleaved caspase-3 by western blot), and measures of translational stress (polysome profiling). **Therapeutic Potential:** As [PELO](/details-gene/53918) is an essential intracellular enzyme-like factor, it is not a suitable target for antibody-based therapies. However, its crucial role in supporting the high translational demands of rapidly proliferating cancer cells makes it a potential target for small molecule inhibitors. A therapeutic strategy would involve inhibition, not activation. Systemic inhibition would likely cause significant toxicity due to the gene's housekeeping functions. Therefore, its therapeutic potential may lie in developing inhibitors with favorable pharmacokinetics for specific tumor types or in combination therapies that allow for lower, less toxic doses while synergizing with drugs that induce proteotoxic or translational stress.

Genular Protein ID: 3567263865

Symbol: PELO_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q9BRX2 Q9GZS6 Q9Y306

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 EMDB 4 Ensembl 1 EvolutionaryTrace 1 GO 20 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 6 PDBsum 6 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11060452

Title: Molecular cloning, expression and chromosome location of the human pelota gene PELO.

PubMed ID: 11060452

DOI: 10.1159/000015667

PubMed ID: 10810093

Title: Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics.

PubMed ID: 10810093

DOI: 10.1101/gr.10.5.703

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18088087

Title: Phosphoproteome of resting human platelets.

PubMed ID: 18088087

DOI: 10.1021/pr0704130

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21448132

Title: Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes.

PubMed ID: 21448132

DOI: 10.1038/emboj.2011.93

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23667253

Title: The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells.

PubMed ID: 23667253

DOI: 10.1074/jbc.m112.448977

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 27543824

Title: Conserved functions of human Pelota in mRNA quality control of nonstop mRNA.

PubMed ID: 27543824

DOI: 10.1002/1873-3468.12366

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 29861391

Title: Ubiquitination of ABCE1 by NOT4 in Response to Mitochondrial Damage Links Co-translational Quality Control to PINK1-Directed Mitophagy.

PubMed ID: 29861391

DOI: 10.1016/j.cmet.2018.05.007

PubMed ID: 32006463

Title: Extraction of mRNA from stalled ribosomes by the Ski complex.

PubMed ID: 32006463

DOI: 10.1016/j.molcel.2020.01.011

PubMed ID: 27863242

Title: Decoding mammalian ribosome-mRNA states by translational GTPase complexes.

PubMed ID: 27863242

DOI: 10.1016/j.cell.2016.10.046

Sequence Information:

  • Length: 385
  • Mass: 43359
  • Checksum: 8A0D264202995B76
  • Sequence:
    • MKLVRKNIEK DNAGQVTLVP EEPEDMWHTY NLVQVGDSLR ASTIRKVQTE SSTGSVGSNR 
VRTTLTLCVE AIDFDSQACQ LRVKGTNIQE NEYVKMGAYH TIELEPNRQF TLAKKQWDSV 
VLERIEQACD PAWSADVAAV VMQEGLAHIC LVTPSMTLTR AKVEVNIPRK RKGNCSQHDR 
ALERFYEQVV QAIQRHIHFD VVKCILVASP GFVREQFCDY LFQQAVKTDN KLLLENRSKF 
LQVHASSGHK YSLKEALCDP TVASRLSDTK AAGEVKALDD FYKMLQHEPD RAFYGLKQVE 
KANEAMAIDT LLISDELFRH QDVATRSRYV RLVDSVKENA GTVRIFSSLH VSGEQLSQLT 
GVAAILRFPV PELSDQEGDS SSEED