Details for: RRP8

Gene ID: 23378

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: RRP8

Ensembl ID: ENSG00000132275

Description: ribosomal RNA processing 8

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • chondrocyte CL0000138
    CSI 29.51
    rCSI 46.93%
    PRS 87.14
  • basal cell of epidermis CL0002187
    CSI 21.31
    rCSI 37.77%
    PRS 63.77
  • helper T cell CL0000912
    CSI 20.04
    rCSI 28.34%
    PRS 87.36
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 19.68
    rCSI 23.85%
    PRS 72.88
  • melanocyte of skin CL1000458
    CSI 17.98
    rCSI 24.51%
    PRS 63.38
  • suprabasal keratinocyte CL4033013
    CSI 15.39
    rCSI 25.12%
    PRS 63.83
  • neural progenitor cell CL0011020
    CSI 8.73
    rCSI 38.42%
    PRS 81.36
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 7.22
    rCSI 17.55%
    PRS 77.19
  • double negative thymocyte CL0002489
    CSI 6.84
    rCSI 4.75%
    PRS 97.58
  • interstitial cell of Cajal CL0002088
    CSI 6.72
    rCSI 8.56%
    PRS 94.45
  • VIP GABAergic cortical interneuron CL4023016
    CSI 6.56
    rCSI 7.83%
    PRS 79.39
  • intermediate monocyte CL0002393
    CSI 5.73
    rCSI 8.64%
    PRS 94.87
  • innate lymphoid cell CL0001065
    CSI 5.29
    rCSI 10.92%
    PRS 85.78
  • rod bipolar cell CL0000751
    CSI 4.68
    rCSI 8.41%
    PRS 86.83
  • CD4-positive helper T cell CL0000492
    CSI 4.47
    rCSI 3.38%
    PRS 97.21
  • cytotoxic T cell CL0000910
    CSI 4.4
    rCSI 25.2%
    PRS 90.33
  • pro-B cell CL0000826
    CSI 4.39
    rCSI 3.64%
    PRS 92.45
  • perivascular cell CL4033054
    CSI 4.05
    rCSI 5.54%
    PRS 94.09
  • neural crest cell CL0011012
    CSI 4.03
    rCSI 3.19%
    PRS 84.96
  • plasmacytoid dendritic cell, human CL0001058
    CSI 4
    rCSI 2.79%
    PRS 94.18
  • naive T cell CL0000898
    CSI 3.93
    rCSI 2.74%
    PRS 98.07
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 3.89
    rCSI 13.98%
    PRS 77.4
  • club cell CL0000158
    CSI 3.71
    rCSI 5.43%
    PRS 87.37
  • epithelial cell of lung CL0000082
    CSI 3.59
    rCSI 2.98%
    PRS 92.13
  • fibroblast of lung CL0002553
    CSI 3.59
    rCSI 3.34%
    PRS 92.69
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 3.41
    rCSI 3.34%
    PRS 97.88
  • enteric smooth muscle cell CL0002504
    CSI 3.35
    rCSI 4.79%
    PRS 91.42
  • erythrocyte CL0000232
    CSI 3.32
    rCSI 7.52%
    PRS 89.55
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.27
    rCSI 2.84%
    PRS 93.32
  • group 3 innate lymphoid cell CL0001071
    CSI 3.22
    rCSI 2.42%
    PRS 94.16
  • common dendritic progenitor CL0001029
    CSI 2.93
    rCSI 3.68%
    PRS 95.49
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.93
    rCSI 4.91%
    PRS 79.35
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.85
    rCSI 10.78%
    PRS 79.52
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.82
    rCSI 4.99%
    PRS 78.76
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 2.81
    rCSI 16.55%
    PRS 79.79
  • megakaryocyte CL0000556
    CSI 2.73
    rCSI 11.85%
    PRS 92.28
  • transit amplifying cell of colon CL0009011
    CSI 2.73
    rCSI 3.21%
    PRS 91.29
  • L6b glutamatergic cortical neuron CL4023038
    CSI 2.54
    rCSI 7.95%
    PRS 80.66
  • common lymphoid progenitor CL0000051
    CSI 2.5
    rCSI 3.34%
    PRS 97.72
  • sncg GABAergic cortical interneuron CL4023015
    CSI 2.4
    rCSI 3.85%
    PRS 80.28
  • ciliated epithelial cell CL0000067
    CSI 2.29
    rCSI 2.02%
    PRS 83.19
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.25
    rCSI 2.04%
    PRS 90.13
  • promyelocyte CL0000836
    CSI 2.11
    rCSI 3.05%
    PRS 93.2
  • common myeloid progenitor CL0000049
    CSI 2.02
    rCSI 1.63%
    PRS 92.37
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.75
    rCSI 3.93%
    PRS 79.74
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.54
    rCSI 4.8%
    PRS 82.3
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.22
    rCSI 3.54%
    PRS 90.65
  • primitive red blood cell CL0002355
    CSI 0.96
    rCSI 5.2%
    PRS 92.67

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.

Comma-separated if multiple.
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 [RRP8](/details-gene/23378) (ribosomal RNA processing 8) is a protein-coding gene located on chromosome 11p15.4. It functions as an S-adenosylmethionine-dependent methyltransferase primarily involved in the processing of ribosomal RNA ([rRNA processing](/details-ontology/GO:0006364)) within the [nucleolus](/details-ontology/GO:0005730). Beyond this core function, [RRP8](/details-gene/23378) plays a significant role in broader cellular processes, including [epigenetic regulation of gene expression](/details-pathway/R-HSA-212165) and the control of cell cycle progression ([Negative regulation of cell cycle](/details-ontology/GO:0045786)). Expression data indicates its heightened importance in metabolically active and highly proliferative cell types, such as [chondrocytes](/details-cell/CL0000138), epidermal cells like [basal cell of epidermis](/details-cell/CL0002187), and various lymphocyte populations, including [helper T cells](/details-cell/CL0000912), suggesting a crucial role in maintaining cellular growth and function. ## Cellular Roles and Expression Landscape The **Overall** expression profile of [RRP8](/details-gene/23378) highlights its significant role across a diverse set of cell types characterized by high rates of proliferation, differentiation, or metabolic activity. Its function appears particularly critical in three main biological systems: * **Structural and Proliferative Tissues:** [RRP8](/details-gene/23378) shows its highest significance in [chondrocytes](/details-cell/CL0000138) (CSI: 29.51), the primary cells of cartilage, and is also highly significant in various skin cells, including [basal cell of epidermis](/details-cell/CL0002187) (CSI: 21.31), [melanocyte of skin](/details-cell/CL1000458) (CSI: 17.98), and [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 15.39). The high demand for protein synthesis to produce extracellular matrix and support tissue turnover in these cells is consistent with a central role for [RRP8](/details-gene/23378) in ribosome biogenesis. * **Immune System:** The gene is a significant marker in several lymphocyte populations, including [helper T cells](/details-cell/CL0000912) (CSI: 20.04), [CD8-positive, alpha-beta memory T cells](/details-cell/CL0001203) (CSI: 19.68), and developing [double negative thymocytes](/details-cell/CL0002489) (CSI: 6.84). This suggests that [RRP8](/details-gene/23378)-mediated ribosome production is essential for the rapid clonal expansion and effector functions of T cells during an immune response. * **Nervous System:** [RRP8](/details-gene/23378) is also notably expressed in [neural progenitor cells](/details-cell/CL0011020) (CSI: 8.73) and mature neurons such as [L2/3-6 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4023040) (CSI: 7.22). Its role in progenitor cells likely supports neurogenesis, while its significance in mature neurons may reflect the high metabolic demands required for maintaining neuronal function and plasticity. ## Pathways and Molecular Function The functional annotations for [RRP8](/details-gene/23378) confirm its identity as a key regulator of ribosome synthesis and cellular metabolism. Its primary molecular function is [S-adenosylmethionine-dependent methyltransferase activity](/details-ontology/GO:0008757), which is central to its role in [rRNA processing](/details-ontology/GO:0006364). This activity takes place predominantly in the [nucleolus](/details-ontology/GO:0005730), a hub for ribosome biogenesis, a finding supported by several proteomic studies ([Link](https://doi.org/10.1091/mbc.e02-05-0271), [Link](https://doi.org/10.1016/s0960-9822(01)00650-9)). [RRP8](/details-gene/23378) is a component of pathways that exert high-level control over cell growth and energy status. It is involved in the [negative epigenetic regulation of rRNA expression](/details-pathway/R-HSA-5250941), indicating it is part of a feedback mechanism that tunes ribosome production to meet cellular demands. This regulatory function connects ribosome synthesis to the cell's energy state, as evidenced by its role in [cellular response to glucose starvation](/details-ontology/GO:0042149) and [energy homeostasis](/details-ontology/GO:0097009) ([Link](https://doi.org/10.1016/j.cell.2008.03.030)). Furthermore, by controlling the rate of protein synthesis, [RRP8](/details-gene/23378) influences major cellular decisions, including cell cycle progression, as shown by its participation in the [negative regulation of cell cycle](/details-ontology/GO:0045786) and the [regulation of G1 to G0 transition](/details-ontology/GO:1903450). ## Research Directions The widespread importance of [RRP8](/details-gene/23378) in regulating cell growth and proliferation suggests several avenues for future research, particularly concerning its role in tissue homeostasis and disease. **Proposed Hypotheses:** 1. Given its high significance in multiple T cell subsets and its function in controlling rRNA synthesis, [RRP8](/details-gene/23378) may act as a critical checkpoint for the metabolic reprogramming and rapid proliferation required for T cell activation and the establishment of immunological memory. 2. The high CSI of [RRP8](/details-gene/23378) in progenitor cells ([basal cell of epidermis](/details-cell/CL0002187), [neural progenitor cell](/details-cell/CL0011020)) coupled with its role in cell cycle regulation suggests that its dynamic downregulation is a prerequisite for cells to exit the cell cycle and undergo terminal differentiation. **Key Experimental Approach:** To test the first hypothesis regarding T cell function, a conditional knockout of [RRP8](/details-gene/23378) could be generated in the T cell lineage (e.g., using a *Cd4-Cre* driver). T cells isolated from these mice could be stimulated *in vitro* with anti-CD3/CD28 antibodies. The impact of [RRP8](/details-gene/23378) deletion would be assessed by measuring key parameters of T cell activation, including proliferation (via CFSE dilution assay), metabolic flux (via Seahorse analysis), and overall protein synthesis capacity (via puromycin incorporation assay). A failure to properly ramp up these processes would confirm the gene's essential role in T cell activation. **Therapeutic Potential:** As a key regulator of ribosome biogenesis, a process frequently dysregulated in cancer to support uncontrolled growth, [RRP8](/details-gene/23378) represents a potential target for anti-proliferative therapies. Inhibition of its methyltransferase activity with a small molecule could selectively impair the growth of cancer cells that are highly dependent on protein synthesis. However, the ubiquitous importance of [RRP8](/details-gene/23378) in healthy proliferating cells (e.g., in the skin and immune system) poses a significant challenge for therapeutic development, as on-target toxicity would be a major concern. A successful therapeutic strategy would likely require tumor-specific drug delivery or exploitation of a therapeutic window where cancer cells are more sensitive to its inhibition than normal tissues.

Genular Protein ID: 2458673027

Symbol: RRP8_HUMAN

Name: Ribosomal RNA-processing protein 8

UniProtKB Accession Codes:

O43159 Q7KZ78 Q9BVM6

Database IDs:

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

Citations:

PubMed ID: 9455477

Title: Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 9455477

DOI: 10.1093/dnares/4.5.307

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: 12429849

Title: Functional proteomic analysis of human nucleolus.

PubMed ID: 12429849

DOI: 10.1091/mbc.e02-05-0271

PubMed ID: 11790298

Title: Directed proteomic analysis of the human nucleolus.

PubMed ID: 11790298

DOI: 10.1016/s0960-9822(01)00650-9

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

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: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

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: 18485871

Title: Epigenetic control of rDNA loci in response to intracellular energy status.

PubMed ID: 18485871

DOI: 10.1016/j.cell.2008.03.030

Sequence Information:

  • Length: 456
  • Mass: 50715
  • Checksum: 49251E2A488DA1C4
  • Sequence:
    • MFEEPEWAEA APVAAGLGPV ISRPPPAASS QNKGSKRRQL LATLRALEAA SLSQHPPSLC 
ISDSEEEEEE RKKKCPKKAS FASASAEVGK KGKKKCQKQG PPCSDSEEEV ERKKKCHKQA 
LVGSDSAEDE KRKRKCQKHA PINSAQHLDN VDQTGPKAWK GSTTNDPPKQ SPGSTSPKPP 
HTLSRKQWRN RQKNKRRCKN KFQPPQVPDQ APAEAPTEKT EVSPVPRTDS HEARAGALRA 
RMAQRLDGAR FRYLNEQLYS GPSSAAQRLF QEDPEAFLLY HRGFQSQVKK WPLQPVDRIA 
RDLRQRPASL VVADFGCGDC RLASSIRNPV HCFDLASLDP RVTVCDMAQV PLEDESVDVA 
VFCLSLMGTN IRDFLEEANR VLKPGGLLKV AEVSSRFEDV RTFLRAVTKL GFKIVSKDLT 
NSHFFLFDFQ KTGPPLVGPK AQLSGLQLQP CLYKRR