| Name | terminal uridylyl transferase 4 |
| Description | Enables RNA uridylyltransferase activity. Involved in RNA metabolic process; stem cell population maintenance; and transposable element silencing by mRNA destabilization. Located in cytoplasmic ribonucleoprotein granule; cytosol; and nucleolus. Implicated in liver benign neoplasm. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTUT4, a noncanonical terminal uridylyl transferase (also known as ZCCHC11), plays a pivotal role in microRNA biogenesis. It is recruited by factors such as Lin28 to select precursor miRNAs—for example, by binding a GGAG motif in pre‐let‑7—to add oligouridine stretches that block Dicer processing and thereby suppress mature let‑7 formation. In other cellular contexts, notably in somatic cells lacking Lin28, TUT4 mono‐uridylates group II pre‑miRNAs to recreate the critical 2‑nucleotide 3′ overhang required for efficient Dicer cleavage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in miRNA maturation, TUT4 collaborates with TUT7 to mark deadenylated mRNAs for decay by selectively uridylating transcripts with short poly(A) tails. This activity contributes to global mRNA turnover and fine‐tunes gene expression programs. Moreover, TUT4‐dependent uridylation is involved in broader post‐transcriptional regulation—it restricts LINE‑1 retrotransposition by modifying their mRNAs and modulates innate immune responses by altering the stability and function of cytokine‐targeting miRNAs that, in turn, impact NF‑κB signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTUT4 activity also has significant implications in cancer biology. By modulating miRNA modifications, TUT4 can alter target recognition—for instance, the addition of a terminal uridine can convert a nonfunctional target site into one that is effectively regulated. Aberrant TUT4-mediated uridylation has been linked to the dysregulation of tumor‐suppressive miRNAs and the consequent activation of oncogenic pathways, contributing both to increased cytokine expression and enhanced metastatic potential. Such findings underscore its emerging role as a modulator of miRNA isoform profiles and a potential therapeutic target in cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Inha Heo, Chirlmin Joo, Young-Kook Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.08.002"}], "href": "https://doi.org/10.1016/j.cell.2009.08.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19703396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19703396"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "James E Thornton, Hao-Ming Chang, Elena Piskounova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.034538.112"}], "href": "https://doi.org/10.1261/rna.034538.112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22898984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22898984"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Inha Heo, Minju Ha, Jaechul Lim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2012.09.022"}], "href": "https://doi.org/10.1016/j.cell.2012.09.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23063654"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23063654"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shuibin Lin, Richard I Gregory "}, {"type": "b", "children": [{"type": "t", "text": "Identification of small molecule inhibitors of Zcchc11 TUTase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15476286.2015.1058478"}], "href": "https://doi.org/10.1080/15476286.2015.1058478"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26114892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26114892"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Christopher R Faehnle, Jack Walleshauser, Leemor Joshua-Tor "}, {"type": "b", "children": [{"type": "t", "text": "Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.3428"}], "href": "https://doi.org/10.1038/nsmb.3428"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28671666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28671666"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jaechul Lim, Minju Ha, Hyeshik Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Uridylation by TUT4 and TUT7 marks mRNA for degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.10.055"}], "href": "https://doi.org/10.1016/j.cell.2014.10.055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25480299"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25480299"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yasumasa Minoda, Kazuko Saeki, Daisuke Aki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel Zinc finger protein, ZCCHC11, interacts with TIFA and modulates TLR signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.04.006"}], "href": "https://doi.org/10.1016/j.bbrc.2006.04.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16643855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16643855"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zbigniew Warkocki, Paweł S Krawczyk, Dorota Adamska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-1s."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2018.07.022"}], "href": "https://doi.org/10.1016/j.cell.2018.07.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30122351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30122351"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Pengcheng Zhang, Mallory I Frederick, Ilka U Heinemann "}, {"type": "b", "children": [{"type": "t", "text": "Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA Homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells11233742"}], "href": "https://doi.org/10.3390/cells11233742"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36497000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36497000"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Matthew R Jones, Lee J Quinton, Matthew T Blahna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zcchc11-dependent uridylation of microRNA directs cytokine expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1931"}], "href": "https://doi.org/10.1038/ncb1931"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19701194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19701194"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "X Fu, Z Meng, W Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-26a enhances miRNA biogenesis by targeting Lin28B and Zcchc11 to suppress tumor growth and metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2013.385"}], "href": "https://doi.org/10.1038/onc.2013.385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24056962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24056962"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Acong Yang, Xavier Bofill-De Ros, Tie-Juan Shao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "3' Uridylation Confers miRNAs with Non-canonical Target Repertoires."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2019.05.014"}], "href": "https://doi.org/10.1016/j.molcel.2019.05.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31178353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31178353"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Anne Gaza, Valerie Fritz, Lara Malek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neo.2021.04.001"}], "href": "https://doi.org/10.1016/j.neo.2021.04.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33901943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33901943"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Ragini Medhi, Jonathan Price, Giulia Furlan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNA uridyl transferases TUT4/7 differentially regulate miRNA variants depending on the cancer cell type."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.078976.121"}], "href": "https://doi.org/10.1261/rna.078976.121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34949722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34949722"}]}]}]}
|
| NCBI Gene ID | 23318 |
| API | |
| Download Associations | |
| Predicted Functions |
 |
| Co-expressed Genes |
|
| Expression in Tissues and Cell Lines |
|
TUT4 has 3,022 functional associations with biological entities spanning 6 categories (chemical, functional term, phrase or reference, disease, phenotype or trait, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 47 datasets.
Click the + buttons to view associations for TUT4 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of TUT4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Carcinogenome Chemical Perturbation Carcinogenicity Signatures | small molecule perturbations changing expression of TUT4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset. | |
| CCLE Cell Line Proteomics | Cell lines associated with TUT4 protein from the CCLE Cell Line Proteomics dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with TUT4 gene from the CellMarker Gene-Cell Type Associations dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of TUT4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of TUT4 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| CM4AI U2OS Cell Map Protein Localization Assemblies | assemblies containing TUT4 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing TUT4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 | cellular components containing TUT4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with TUT4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| DeepCoverMOA Drug Mechanisms of Action | small molecule perturbations with high or low expression of TUT4 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by TUT4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with TUT4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with TUT4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with TUT4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving TUT4 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving TUT4 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2023 | cellular components containing TUT4 protein from the curated GO Cellular Component Annotations 2023 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing TUT4 protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by TUT4 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by TUT4 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of TUT4 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of TUT4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue-Specific Aging Signatures | tissue samples with high or low expression of TUT4 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with TUT4 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by TUT4 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of TUT4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of TUT4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of TUT4 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| LINCS L1000 CMAP CRISPR Knockout Consensus Signatures | gene perturbations changing expression of TUT4 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by TUT4 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MoTrPAC Rat Endurance Exercise Training | tissue samples with high or low expression of TUT4 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset. | |
| NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles | drug perturbations changing expression of TUT4 gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving TUT4 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving TUT4 protein from the Wikipathways PFOCR 2024 dataset. | |
| Reactome Pathways 2024 | pathways involving TUT4 protein from the Reactome Pathways 2024 dataset. | |
| Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of TUT4 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset. | |
| Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of TUT4 gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset. | |
| Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of TUT4 gene from the Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of TUT4 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of TUT4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of TUT4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Sci-Plex Drug Perturbation Signatures | drug perturbations changing expression of TUT4 gene from the Sci-Plex Drug Perturbation Signatures dataset. | |
| Tahoe Therapeutics Tahoe 100M Perturbation Atlas | drug perturbations changing expression of TUT4 gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of TUT4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of TUT4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with TUT4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
