Details for: RPUSD2

Gene ID: 27079

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: RPUSD2

Ensembl ID: ENSG00000166133

Description: RNA pseudouridine synthase domain containing 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 3.93
    rCSI 2.62%
    PRS 99.67
  • club cell CL0000158
    CSI 2.26
    rCSI 3.32%
    PRS 99.49
  • retinal cone cell CL0000573
    CSI 2.05
    rCSI 3.3%
    PRS 97.75

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

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  • Node Color (Target Cell CSI, relative to current network):
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  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
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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 [RPUSD2](/details-gene/27079) (RNA pseudouridine synthase domain containing 2) is a protein-coding gene located on chromosome 15q15.1. Functionally, [RPUSD2](/details-gene/27079) is an RNA-binding enzyme with pseudouridine synthase activity, involved in the post-transcriptional modification of both ribosomal RNA (rRNA) and messenger RNA (mRNA) as supported by its annotation for [GO:0000455](https://www.ebi.ac.uk/QuickGO/term/GO:0000455) and [GO:1990481](https://www.ebi.ac.uk/QuickGO/term/GO:1990481). This modification, termed pseudouridylation, is critical for RNA processing, stability, and translational efficiency [Link](https://doi.org/10.1016/j.molcel.2021.12.023). Expression analysis indicates that while its function is fundamental, its significance is particularly pronounced in a diverse set of specialized cells, including cytotoxic immune cells like [CD16-positive, CD56-dim natural killer cells](/details-cell/CL0000939), secretory epithelial cells such as [club cells](/details-cell/CL0000158), and photoreceptor [retinal cone cells](/details-cell/CL0000573). ## Cellular Roles and Expression Landscape The expression profile of [RPUSD2](/details-gene/27079) highlights its importance in functionally diverse and highly active cell types, suggesting a role in maintaining specialized cellular processes through RNA modification. **Overall**, the gene shows its highest significance in [CD16-positive, CD56-dim natural killer cells, human](/details-cell/CL0000939) (CSI: 3.93), a major component of the innate immune system responsible for cytotoxic activity. This suggests that [RPUSD2](/details-gene/27079) may be crucial for the rapid synthesis or stability of transcripts encoding effector proteins in these cells. Beyond the immune system, [RPUSD2](/details-gene/27079) is also a significant gene in secretory [club cells](/details-cell/CL0000158) of the lung (CSI: 2.26) and in [retinal cone cells](/details-cell/CL0000573) (CSI: 2.05). [Club cells](/details-cell/CL0000158) have a high protein secretion burden, while [retinal cone cells](/details-cell/CL0000573) are metabolically active and require robust protein synthesis for phototransduction. The elevated significance of [RPUSD2](/details-gene/27079) in these distinct contexts points towards a conserved role in supporting cells with high translational demand or those that rely on the precise regulation of specific mRNA transcripts for their core function. ## Pathways and Molecular Function The functional annotations for [RPUSD2](/details-gene/27079) confirm its identity as an RNA-modifying enzyme. Its primary molecular function is defined as pseudouridine synthase activity ([GO:0009982](https://www.ebi.ac.uk/QuickGO/term/GO:0009982)) and RNA binding ([GO:0003723](https://www.ebi.ac.uk/QuickGO/term/GO:0003723)). These activities contribute to several key biological processes. The gene is directly implicated in the modification of both rRNA and mRNA. Its involvement in enzyme-directed rRNA pseudouridine synthesis ([GO:0000455](https://www.ebi.ac.uk/QuickGO/term/GO:0000455)) suggests a role in ribosome biogenesis and function, which would be critical in cells with high protein synthesis rates like [club cells](/details-cell/CL0000158) and [retinal cone cells](/details-cell/CL0000573). Furthermore, its role in mRNA pseudouridine synthesis ([GO:1990481](https://www.ebi.ac.uk/QuickGO/term/GO:1990481)) and the broader process of mRNA processing ([GO:0006397](https://www.ebi.ac.uk/QuickGO/term/GO:0006397)) indicates it can fine-tune gene expression by affecting mRNA stability, splicing, or translation. This latter function is supported by recent research showing that pseudouridine synthases can modify pre-mRNA co-transcriptionally to affect its subsequent processing [Link](https://doi.org/10.1016/j.molcel.2021.12.023). This mechanism could be particularly important for regulating the expression of cytotoxic effector molecules in [natural killer cells](/details-cell/CL0000939). ## Research Directions The diverse cellular contexts where [RPUSD2](/details-gene/27079) is significant, combined with its fundamental role in RNA biology, opens several avenues for future investigation. **Proposed Hypotheses:** 1. **Regulation of NK Cell Cytotoxicity:** Given its top ranking in [CD16-positive, CD56-dim natural killer cells](/details-cell/CL0000939), it is hypothesized that [RPUSD2](/details-gene/27079)-mediated pseudouridylation of specific mRNAs (e.g., *GZMB*, *PRF1*, *IFNG*) is essential for their stability and rapid translation upon cell activation, thereby controlling the cytotoxic potential of NK cells. 2. **Maintenance of Airway Homeostasis:** In [club cells](/details-cell/CL0000158), it is hypothesized that [RPUSD2](/details-gene/27079) is required for the efficient processing and translation of transcripts encoding key secretory proteins (e.g., SCGB1A1). Dysfunction of [RPUSD2](/details-gene/27079) in these cells may compromise the airway's protective mucosal layer, contributing to respiratory diseases. 3. **Photoreceptor Survival:** The high significance of [RPUSD2](/details-gene/27079) in [retinal cone cells](/details-cell/CL0000573) suggests a hypothesis that its activity is critical for maintaining ribosomal fidelity and the efficient synthesis of proteins involved in the phototransduction cascade. Loss of [RPUSD2](/details-gene/27079) could lead to proteotoxic stress and contribute to the pathology of retinal degenerative disorders. **Experimental Approach:** To test the hypothesis regarding the role of [RPUSD2](/details-gene/27079) in NK cell function (Hypothesis 1), a targeted experiment could be performed. CRISPR-Cas9-mediated knockout of [RPUSD2](/details-gene/27079) in a human NK cell line (e.g., NK-92) or in primary human NK cells would be the first step. These knockout cells and control cells would then be co-cultured with target tumor cells (e.g., K562). The impact on NK cell function could be assessed by measuring cytotoxicity through flow cytometry-based assays and quantifying cytokine release (e.g., IFN-gamma) via ELISA. To identify direct mRNA targets, techniques such as pseudo-seq or RIP-seq combined with RNA sequencing could be employed to map [RPUSD2](/details-gene/27079)-dependent pseudouridylation sites transcriptome-wide and determine how their absence affects mRNA translation and stability. **Therapeutic Potential:** As an intracellular enzyme involved in a fundamental biological process, targeting [RPUSD2](/details-gene/27079) systemically presents a challenge due to potential on-target toxicities in healthy, highly active tissues like the retina and lungs. However, its role in specific cell types suggests context-dependent therapeutic opportunities. For instance, in malignancies derived from cell types where it is highly active, such as NK-cell leukemia, inhibition of [RPUSD2](/details-gene/27079) could be a viable anti-proliferative strategy. Conversely, in degenerative diseases potentially caused by its reduced function, such as certain retinopathies, therapeutic approaches aimed at augmenting its activity might be beneficial. Therefore, its potential as a therapeutic target is highly dependent on the specific disease pathology and would likely require cell-type-specific delivery systems to achieve a favorable therapeutic window.

Genular Protein ID: 984322226

Symbol: RUSD2_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8IZ73 B4DDD1 Q7L989 Q92939 Q96IA7 Q96N50

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 2 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 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 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 Rhea 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

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: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 31477916

Title: mRNA structure determines modification by pseudouridine synthase 1.

PubMed ID: 31477916

DOI: 10.1038/s41589-019-0353-z

PubMed ID: 35051350

Title: Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing.

PubMed ID: 35051350

DOI: 10.1016/j.molcel.2021.12.023

Sequence Information:

  • Length: 545
  • Mass: 61311
  • Checksum: 16E8B71918A6E0B7
  • Sequence:
    • MWLDRRGWLR VLGHWRYDLR RPSFTRTWSG DKGPMAETVS TQVGTEGGLR ASHQQNGDAG 
GDAKVELSPG PPKPAGREVE PAPVGGEHPS AAAPGPGKHK KRRGATRERV VPPPKKRRTG 
VSFGDEHFAE TSYYFEGGLR KVRPYYFDFR TYCKGRWVGH SLLHVFSTEF RAQPLAYYEA 
AVRAGRLQLN EKPVQDLNIV LKDNDFLRNT VHRHEPPVTA EPIRLLAENE DVVVVDKPSS 
IPVHPCGRFR HNTVIFILGK EHQLKELHPL HRLDRLTSGV LMFAKTAAVS ERIHEQVRDR 
QLEKEYVCRV EGEFPTEEVT CKEPILVVSY KVGVCRVDPR GKPCETVFQR LSYNGQSSVV 
RCRPLTGRTH QIRVHLQFLG HPILNDPIYN SVAWGPSRGR GGYIPKTNEE LLRDLVAEHQ 
AKQSLDVLDL CEGDLSPGLT DSTAPSSELG KDDLEELAAA AQKMEEVAEA APQELDTIAL 
ASEKAVETDV MNQETDPLCA ECRLVRQDPL PQDLVMFLHA LRYKGPGFEY FSPMPAWAQD 
DWQKD