Accession ID: MIRT003215 [miRNA, hsa-miR-421 ::
ATM, target gene]
| pre-miRNA ID | hsa-mir-421 LinkOut: [miRBase ] |
|---|---|
| Synonyms | MIRN421, hsa-mir-421, MIR421 |
| Description | Homo sapiens miR-421 stem-loop |
| 2nd Structure of pre-miRNA |  |
| Mature miRNA | hsa-miR-421 |
|---|---|
| Mature Sequence | 48| AUCAACAGACAUUAAUUGGGCGC |70 |
| Evidence | Experimental |
| Experiments | Microarray |
| Putative hsa-miR-421 Targets | LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ] |
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| Gene Symbol | ATM LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ] | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Synonyms | AT1, ATA, ATC, ATD, ATDC, ATE, DKFZp781A0353, MGC74674, TEL1, TELO1 | ||||||||||||||||||||
| Description | ataxia telangiectasia mutated | ||||||||||||||||||||
| Transcript | NM_000051 LinkOut: [ RefSeq ] | ||||||||||||||||||||
| Other Transcripts | NM_138292 | ||||||||||||||||||||
| Expression | LinkOut: [ BioGPS ] | ||||||||||||||||||||
| KEGG Pathway |
hsa04110 Cell cycle - Homo sapiens (human) hsa04115 p53 signaling pathway - Homo sapiens (human) hsa04210 Apoptosis - Homo sapiens (human) |
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| Putative miRNA Targets on ATM | LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ] | ||||||||||||||||||||
| 3'UTR of ATM (miRNA target sites are highlighted) |
>ATM|NM_000051|3'UTR 1 TGATCTTCAGTATATGAATTACCCTTTCATTCAGCCTTTAGAAATTATATTTTAGCCTTTATTTTTAACCTGCCAACATA 81 CTTTAAGTAGGGATTAATATTTAAGTGAACTATTGTGGGTTTTTTTGAATGTTGGTTTTAATACTTGATTTAATCACCAC 161 TCAAAAATGTTTTGATGGTCTTAAGGAACATCTCTGCTTTCACTCTTTAGAAATAATGGTCATTCGGGCTGGGCGCAGCG 241 GCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGTGAGCGGATCACAAGGTCAGGAGTTCGAGACCAGCCTGGCCA 321 AGAGACCAGCCTGGCCAGTATGGTGAAACCCTGTCTCTACTAAAAATACAAAAATTAGCCGAGCATGGTGGCGGGCACCT 401 GTAATCCCAGCTACTCGAGAGGCTGAGGCAGGAGAATCTCTTGAACCTGGGAGGTGAAGGTTGCTGTGGGCCAAAATCAT 481 GCCATTGCACTCCAGCCTGGGTGACAAGAGCGAAACTCCATCTCAAAAAAAAAAAAAAAAAAACAGAAACGTATTTGGAT 561 TTTTCCTAGTAAGATCACTCAGTGTTACTAAATAATGAAGTTGTTATGGAGAACAAATTTCAAAGACACAGTTAGTGTAG 641 TTACTATTTTTTTAAGTGTGTATTAAAACTTCTCATTCTATTCTCTTTATCTTTTAAGCCCTTCTGTACTGTCCATGTAT 721 GTTATCTTTCTGTGATAACTTCATAGATTGCCTTCTAGTTCATGAATTCTCTTGTCAGATGTATATAATCTCTTTTACCC 801 TATCCATTGGGCTTCTTCTTTCAGAAATTGTTTTTCATTTCTAATTATGCATCATTTTTCAGATCTCTGTTTCTTGATGT 881 CATTTTTAATGTTTTTTTAATGTTTTTTATGTCACTAATTATTTTAAATGTCTGTACTTGATAGACACTGTAATAGTTCT 961 ATTAAATTTAGTTCCTGCTGTTTATATCTGTTGATTTTTGTATTTGATAGGCTGTTCATCCAGTTTTGTCTTTTTGAAAA 1041 GTGAGTTTATTTTCAGCAAGGCTTTATCTATGGGAATCTTGAGTGTCTGTTTATGTCATATTCCCAGGGCTGTTGCTGCA 1121 CACAAGCCCATTCTTATTTTAATTTCTTGGCTTTAGGGTTTCCATACCTGAAGTGTAGCATAAATACTGATAGGAGATTT 1201 CCCAGGCCAAGGCAAACACACTTCCTCCTCATCTCCTTGTGCTAGTGGGCAGAATATTTGATTGATGCCTTTTTCACTGA 1281 GAGTATAAGCTTCCATGTGTCCCACCTTTATGGCAGGGGTGGAAGGAGGTACATTTAATTCCCACTGCCTGCCTTTGGCA 1361 AGCCCTGGGTTCTTTGCTCCCCATATAGATGTCTAAGCTAAAAGCCGTGGGTTAATGAGACTGGCAAATTGTTCCAGGAC 1441 AGCTACAGCATCAGCTCACATATTCACCTCTCTGGTTTTTCATTCCCCTCATTTTTTTCTGAGACAGAGTCTTGCTCTGT 1521 CACCCAGGCTGGAGTGCAGTGGCATGATCTCAGCTCACTGAAACCTCTGCCTCCTGGGTTCAAGCAATTCTCCTGCCTCA 1601 GCCTCCCGAGTAGCTGGGACTACAGGCGTGTGCCAACACGCCCGGCTAATTTTTTGTATTTTTATTAGAGACGGAGTTTC 1681 ACCGTGTTAGCCAGGATGGTCTCGATCGCTTGACCTCGTGATCCACCCTCCTCGGCCTCCCAAAGTGCTGGGATTACAGG 1761 TGTGAGCCACCGCGCCCGGCCTCATTCCCCTCATTTTTGACCGTAAGGATTTCCCCTTTCTTGTAAGTTCTGCTATGTAT 1841 TTAAAAGAATGTTTTCTACATTTTATCCAGCATTTCTCTGTGTTCTGTTGGAAGGGAAGGGCTTAGGTATCTAGTTTGAT 1921 ACATAGGTAGAAGTGGAACATTTCTCTGTCCCCCAGCTGTCATCATATAAGATAAACATCAGATAAAAAGCCACCTGAAA 2001 GTAAAACTACTGACTCGTGTATTAGTGAGTATAATCTCTTCTCCATCCTTAGGAAAATGTTCATCCCAGCTGCGGAGATT 2081 AACAAATGGGTGATTGAGCTTTCTCCTCGTATTTGGACCTTGAAGGTTATATAAATTTTTTTCTTATGAAGAGTTGGCAT 2161 TTCTTTTTATTGCCAATGGCAGGCACTCATTCATATTTGATCTCCTCACCTTCCCCTCCCCTAAAACCAATCTCCAGAAC 2241 TTTTTGGACTATAAATTTCTTGGTTTGACTTCTGGAGAACTGTTCAGAATATTACTTTGCATTTCAAATTACAAACTTAC 2321 CTTGGTGTATCTTTTTCTTACAAGCTGCCTAAATGAATATTTGGTATATATTGGTAGTTTTATTACTATAGTAAATCAAG 2401 GAAATGCAGTAAACTTAAAATGTCTTTAAGAAAGCCCTGAAATCTTCATGGGTGAAATTAGAAATTATCAACTAGATAAT 2481 AGTATAGATAAATGAATTTGTAGCTAATTCTTGCTAGTTGTTGCATCCAGAGAGCTTTGAATAACATCATTAATCTACTC 2561 TTTAGCCTTGCATGGTATGCTATGAGGCTCCTGTTCTGTTCAAGTATTCTAATCAATGGCTTTGAAAAGTTTATCAAATT 2641 TACATACAGATCACAAGCCTAGGAGAAATAACTAATTCACAGATGACAGAATTAAGATTATAAAAGATTTTTTTTTTGTA 2721 ATTTTAGTAGAGACAGGGTTGCCATTGTATTCCAGCCTTGGCGACAGAGCAAGACTCTGCCTCAAAAAAAAAAAAAAAAA 2801 GGTTTTGGCAAGCTGGAACTCTTTCTGCAAATGACTAAGATAGAAAACTGCCAAGGACAAATGAGGAGTAGTTAGATTTT 2881 GAAAATATTAATCATAGAATAGTTGTTGTATGCTAAGTCACTGACCCATATTATGTACAGCATTTCTGATCTTTACTTTG 2961 CAAGATTAGTGATACTATCCCAATACACTGCTGGAGAAATCAGAATTTGGAGAAATAAGTTGTCCAAGGCAAGAAGATAG 3041 TAAATTATAAGTACAAGTGTAATATGGACAGTATCTAACTTGAAAAGATTTCAGGCGAAAAGAATCTGGGGTTTGCCAGT 3121 CAGTTGCTCAAAAGGTCAATGAAAACCAAATAGTGAAGCTATCAGAGAAGCTAATAAATTATAGACTGCTTGAACAGTTG 3201 TGTCCAGATTAAGGGAGATAATAGCTTTCCCACCCTACTTTGTGCAGGTCATACCTCCCCAAAGTGTTTACCTAATCAGT 3281 AGGTTCACAAACTCTTGGTCATTATAGTATATGCCTAAAATGTATGCACTTAGGAATGCTAAAAATTTAAATATGGTCTA 3361 AAGCAAATAAAAGCAAAGAGGAAAAACTTTGGACAGCGTAAAGACTAGAATAGTCTTTTAAAAAGAAAGCCAGTATATTG 3441 GTTTGAAATATAGAGATGTGTCCCAATTTCAAGTATTTTAATTGCACCTTAATGAAATTATCTATTTTCTATAGATTTTA 3521 GTACTATTGAATGTATTACTTTACTGTTACCTGAATTTATTATAAAGTGTTTTTGAATAAATAATTCTAAAAGC Target sites Provided by authors Predicted by miRanda |
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| miRNA-target interactions (Predicted by miRanda) |
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| miRNA:Target | hsa-miR-421 :: ATM [ Functional MTI ] | ||||||
|---|---|---|---|---|---|---|---|
| Validation Method | Luciferase reporter assay , qRT-PCR , Western blot | ||||||
| Conditions | HeLa | ||||||
| Location of target site | 3'UTR | ||||||
| Tools used in this research | microCOSm | ||||||
| Original Description (Extracted from the article) | ... A signii??cant reduction (30%) in the luciferase activity of the reporter construct containing the ATM 3`UTR was observed in the presence of miR-421, whereas no changes were noted in the luciferase activity of the unmodii??ed construct (pRL) with miR-421 expression (Fig. 1C). ... - Hu, H. Du, L. Nagabayashi, G. Seeger, R. C. et al., 2010, Proc Natl Acad Sci U S A. |
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| miRNA-target interactions (Provided by authors) |
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| Article |
- Hu, H.
Du, L.
Nagabayashi, G.
Seeger, R. C. et al. - Proc Natl Acad Sci U S A, 2010
Ataxia-telangiectasia mutated (ATM) is a high molecular weight protein serine/threonine kinase that plays a central role in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of DNA double-strand breaks. Little is known about the regulatory mechanisms for ATM expression itself. MicroRNAs are naturally existing regulators that modulate gene expression in a sequence-specific manner. Here, we show that a human microRNA, miR-421, suppresses ATM expression by targeting the 3'-untranslated region (3'UTR) of ATM transcripts. Ectopic expression of miR-421 resulted in S-phase cell cycle checkpoint changes and an increased sensitivity to ionizing radiation, creating a cellular phenotype similar to that of cells derived from ataxia-telangiectasia (A-T) patients. Blocking the interaction between miR-421 and ATM 3'UTR with an antisense morpholino oligonucleotide rescued the defective phenotype caused by miR-421 overexpression, indicating that ATM mediates the effect of miR-421 on cell cycle checkpoint and radiosensitivity. Overexpression of the N-Myc transcription factor, an oncogene frequently amplified in neuroblastoma, induced miR-421 expression, which, in turn, down-regulated ATM expression, establishing a linear signaling pathway that may contribute to N-Myc-induced tumorigenesis in neuroblastoma. Taken together, our findings implicate a previously undescribed regulatory mechanism for ATM expression and ATM-dependent DNA damage response and provide several potential targets for treating neuroblastoma and perhaps A-T.
LinkOut: [PMID: 20080624]
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