| pre-miRNA Information | |
|---|---|
| pre-miRNA | hsa-mir-1539 |
| Genomic Coordinates | chr18: 49487373 - 49487422 |
| Synonyms | MIRN1539, hsa-mir-1539, MIR1539 |
| Description | Homo sapiens miR-1539 stem-loop |
| Comment | None |
| RNA Secondary Structure |  |
| Mature miRNA Information | ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mature miRNA | hsa-miR-1539 | |||||||||||||||||||||||||||
| Sequence | 30| UCCUGCGCGUCCCAGAUGCCC |50 | |||||||||||||||||||||||||||
| Evidence | Experimental | |||||||||||||||||||||||||||
| Experiments | ChIP-seq | DRVs in miRNA |
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| SNPs in miRNA |
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| Putative Targets | ||||||||||||||||||||||||||||
| miRNA Expression profile | |
|---|---|
| Human miRNA Tissue Atlas | |
| Circulating MicroRNA Expression Profiling | |
| Gene Information | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene Symbol | CTC1 | ||||||||||||||||||||
| Synonyms | AAF-132, AAF132, C17orf68, CRMCC, tmp494178 | ||||||||||||||||||||
| Description | CST telomere replication complex component 1 | ||||||||||||||||||||
| Transcript | NM_025099 | ||||||||||||||||||||
| Expression | |||||||||||||||||||||
| Putative miRNA Targets on CTC1 | |||||||||||||||||||||
| 3'UTR of CTC1 (miRNA target sites are highlighted) |
>CTC1|NM_025099|3'UTR 1 CTGAACTGCAAGGATGGCCTGAGAGTCCTTCCTTGCTGAAAACCTGAAGGCCTAGGTCCTGGCTCCTCTCCCTACTTGTT 81 CTGTGATTGAACCAAGGACTCCAGATTCACAAACTGCTACTCCACTATAATTTCCCTTCTTTGGTGTTCTGGTGCCAGCC 161 TGCCTTGGCAAAATTGTGGCAACAGGAAATCATGGCCCTATTAATATGTCCTCTGATTGGGACAAGGCACCTGCATTCAC 241 AGGCGGCCCTGAGCACCTGGGTTCTGACTTTGTCGCAGGAGCTGAGGGAACAAAAGACTTGCTCGCTGTGGGGTGATGGT 321 GACAGGCCTATTGACCTGCAATGAAGCCCTCTGGTGTCATTTCTCACTGGTACTCATCTCTGGGGTCCCAGGCCTCCTGA 401 CTCCTAGTTGTCCACCTCCTAGGAACTCCTAGTCGTTCATCATCATTTCAGCCCTTTGCCGCCAGGGCCAAAGGTGGAAA 481 GTGATTTGGAAGAGAAGAGCTTTTCGTCCAGCAGAAGAAATGGTACCAAAATCAGTCTGTAAAGGAAGTAAATTGGGGAG 561 TTGGCGGCAAGGCAGAGAGCATAGCTATGATGGTCTCAGTCAGTAAGGCTGGGCCCTGCAGGAAGTCAAATATGAATGCC 641 TAGAGGTGTTCACAAGCACAAAGAAGGTGTAGGGGGAGGCAAGTGCCAGGCACAAGCAGGGGCAGGTGAGGACTCTGGGT 721 GACTGTGCTATAGGGCCCCAGGCTACGGTTAGCCCTGTAGGTTTCCCAAGGGCCTGGCCTAAGGCAGATCCTTGATCGAT 801 ATACCTTGAGACCAGAAGGTGCTCCGAAATCACAACCGTACAATTAGGGGATCTAGGAACAATTCTTTGGAGATACCAAT 881 GCCTTTGGCTGGTGTTGCTGCATTTCTTTACTGGGGACTGATAGATGGAGAGGTGGAAAGATGAGCTGAGGCACATCTTT 961 CAGAGCTACTGGGAGGCCATTTCTTCCTGGCTGTTAGGATTTGTTCGTGTTTGGGAGACCTTTAGAGCGTGGTTAAACCC 1041 ATATGTTGGGATTTATGCTGCTTTTATGGTAGCAATACCCTATATTAAGATTTGAAGTAGACCCGGAAAGTTAGTGGCCG 1121 GTTAGCTCAGTTGGTTAGAGCGTGGTGCTAATAACGCCAAGGTCGCGGGTTCGAACCCCGTACGGGCCAGTGGGTGGCTT 1201 TTTTTTGTGTGTGTTTTGTTTTCTGACCCTCTGCTGTTATCCGGAAGTTTCTACCCGGAGCCAGTTGCCTTCTGGTAACA 1281 GAATTATATTGCACCTACTGCTTCCTATTCCCTGAATCACTAGCGCTCCCGAAGGCTTGGAGGGAGGAGTCTCTGGGCAC 1361 CCGGGTGAAAGGAAGGTTCACGTGCAACCGCCGCGTCTTTTTTTCCCTGAAGCGCTTTCATGGAGGCAGATGTTTGTCAG 1441 TCAAGGGAAGTAAGAAAGGCATTGGATGAAAACGAAGCCCTAAGCCTCGTAGTCGTGGCCGAGTGGTTAAGGCGATGGAC 1521 TAGAAATCCATTGGGGTCTCCCCGCGCAGGTTCGAATCCTGCCGACTACGTCATATTTTTTTCTTCAGCATACTGACCAT 1601 ATTTCTCTCCAGGATGGGATGATCCAGTCGGCACCCTCCAAACCTCTCATCTAGGAACTCTAGAATCGAGAATTTGATTT 1681 AGAGTCTATGATTTTGGTTTGAAATCTATGATTAACGTCTTTGGACATTGAAGGAAATCCGAGGAATGGACAAGTGATGC 1761 AAGAGCCAGTTGAGTTACCAAATTAGTTCTAGAAAGATCTGAAAAAGCTCGGTCCGGGTTCCTAGCTCTATATTCTTGTA 1841 GATGAATTTCAGGAACCTTTATGGCAGCTTCGGCGCCGTGGCTTAGTTGGTTAAAGCGCCTGTCTAGTAAACAGGAGATC 1921 CTGGGTTCGAATCCCAGCGGTGCCTTTATTCAATTGAAACAGCGTGATTTTGCGGCTAAATCCACATCCTTTCATGTATT 2001 GTTTTTATATCAGAACGCGTAAGAGTTTCTGTTCTGCACTCATAGCACCCACATTTCCTGCAGAGTCAAGCTGCCACTCC 2081 CATGAGATCGCCACTCTAAAAGGTGGTTCTCTAACTTAGGGGCAGAAATGTTGCATAGGCCTAAGGGTCCTTTGCTTAAC 2161 TGATGCCACACCCCACTGGTGCAGGTGGACTGGGTCAGGCGGCCGCCCCACCCTCGATGGAAGGGGCTGCCCACCTTCCA 2241 GGCCTCTTTCTCCACCCTAGGACGTCCCCTAGAACCTGAGCCACTTTGTTTTGTTTGGCTCTTCATTATAGTTCTTTGGG 2321 TTTGGTGGCTCATAATGTTATATATATAGTATATAATATAAAAATATATATTTAAATATACAGTATTTAAAATTTGGCAC 2401 AGCTTCCAGATGCGGTCCTCTAACTGGTCTTTCACTTGCAGTTACCTCCATCCCTCTCCACCAGCGGGATGTCAGGGTAA 2481 GGAGTAAGCAGGGATCCGGCTGGCCTGGCCTGGCCTGGCACCAGGTTTCGTGCAGCAGGGTGCAGAAGGGCTGAGGCCAT 2561 GTGAACAGAGTCCAAGAAAGCATCATTCGGGAGTCGCTAGGGATCCTGGTGTGGAAGGGCAGGGCACTTTTCTGGAGCAC 2641 TGAAGCTAGGCTGGTTAAGGAAGAAATAAATGCCAGAGATAAGGCAAGAAATAGGATCTGTGAGCTCTTGGCAGGACCTA 2721 AACCTCCTTGGAAGATAGGCAGAAAGCTCTCGACACCATTCCATGGCCCACGAACCAATGTAAGATGAGCAAATGGCTTG 2801 AAGGAATTGCTACCTCCAGGTCAAGCCAGGGATGCAGCACTGCCGAGACCACGTTTGTGCCAAGCACTGGGCTGGACCCT 2881 GTGCAGAACCAAATGAACAAGGCACGTTCCCCTTTCAGCACTAACGGCACTGTAAGAACAGGGAGAAGTGGAATCTAATC 2961 TGGCCTGAGGGTAGAGGGTGATCAGCTAAGTCTGAAACACCATGTAGAAACTTGCCATGTATGGCCGGGCGCGGTGGCTC 3041 ACGCCTGTAATCCCAGCGCTTTGGGAGGCCAAGGTGGGCGGATCACGAGGTCAGGAGTTCCAGACCAGCAGCCTGGCCAA 3121 CATAGTGAAACCTGGTAACATAGTGAAACCTCGTCTCTACTAAAAATGCAAAAAATTAGCCAGGCGTGGTGGCAGGCGCC 3201 TGCAGTCCTAGCTACTTGGGAGGCTGAGGCAAGAGAATCGCTTCAACCTTGGAGGGGGGAGGAGGTGTTGTCAGCCGAGA 3281 TCGCGCCACTGCATCCCAGCCTGGGCAACAAGAGTGAAACTCCGTCTCAAAAAAATGAAATAAAATAAACGAATGATCAA 3361 AAAAAAAAAAAAAAAA Target sites
Provided by authors
Predicted by miRanda
DRVs
SNPs
DRVs & SNPs
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| miRNA-target interactions (Predicted by miRanda) |
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| DRVs in gene 3'UTRs | |||||||||||||||||||||
| SNPs in gene 3'UTRs | |||||||||||||||||||||
| Experimental Support 1 for Functional miRNA-Target Interaction | |
|---|---|
| miRNA:Target | ---- |
| Validation Method |
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| Conditions | HEK293 |
| Location of target site | 3'UTR |
| Tools used in this research | TargetScan , miRTarCLIP , Piranha |
| Original Description (Extracted from the article) |
...
PAR-CLIP data was present in GSM545212. RNA binding protein: AGO1. Condition:Control
PAR-CLIP data was present in GSM545215. RNA binding protein: AGO4. Condition:Control
PAR-CLIP data was present in GSM545217. RNA binding protein: AGO2. Condition:miR-7 transfection
... - Hafner M; Landthaler M; Burger L; Khorshid et al., 2010, Cell. |
| Article |
- Hafner M; Landthaler M; Burger L; Khorshid et al. - Cell, 2010
RNA transcripts are subject to posttranscriptional gene regulation involving hundreds of RNA-binding proteins (RBPs) and microRNA-containing ribonucleoprotein complexes (miRNPs) expressed in a cell-type dependent fashion. We developed a cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs. The crosslinked sites are revealed by thymidine to cytidine transitions in the cDNAs prepared from immunopurified RNPs of 4-thiouridine-treated cells. We determined the binding sites and regulatory consequences for several intensely studied RBPs and miRNPs, including PUM2, QKI, IGF2BP1-3, AGO/EIF2C1-4 and TNRC6A-C. Our study revealed that these factors bind thousands of sites containing defined sequence motifs and have distinct preferences for exonic versus intronic or coding versus untranslated transcript regions. The precise mapping of binding sites across the transcriptome will be critical to the interpretation of the rapidly emerging data on genetic variation between individuals and how these variations contribute to complex genetic diseases.
LinkOut: [PMID: 20371350]
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| Experimental Support 2 for Functional miRNA-Target Interaction | |
|---|---|
| miRNA:Target | ---- |
| Validation Method |
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| Conditions | HEK293 |
| Disease | 80169.0 |
| Location of target site | 3'UTR |
| Tools used in this research | TargetScan , miRTarCLIP , Piranha |
| Original Description (Extracted from the article) |
...
"HITS-CLIP data was present in GSM714642. RNA binding protein: AGO2. Condition:completeT1
"PAR-CLIP data was present in GSM714645. RNA binding protein: AGO2. Condition:completeT1
... - Kishore S; Jaskiewicz L; Burger L; Hausser et al., 2011, Nature methods. |
| Article |
- Kishore S; Jaskiewicz L; Burger L; Hausser et al. - Nature methods, 2011
Cross-linking and immunoprecipitation (CLIP) is increasingly used to map transcriptome-wide binding sites of RNA-binding proteins. We developed a method for CLIP data analysis, and applied it to compare CLIP with photoactivatable ribonucleoside-enhanced CLIP (PAR-CLIP) and to uncover how differences in cross-linking and ribonuclease digestion affect the identified sites. We found only small differences in accuracies of these methods in identifying binding sites of HuR, which binds low-complexity sequences, and Argonaute 2, which has a complex binding specificity. We found that cross-link-induced mutations led to single-nucleotide resolution for both PAR-CLIP and CLIP. Our results confirm the expectation from original CLIP publications that RNA-binding proteins do not protect their binding sites sufficiently under the denaturing conditions used during the CLIP procedure, and we show that extensive digestion with sequence-specific RNases strongly biases the recovered binding sites. This bias can be substantially reduced by milder nuclease digestion conditions.
LinkOut: [PMID: 21572407]
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| Experimental Support 3 for Functional miRNA-Target Interaction | |
|---|---|
| miRNA:Target | ---- |
| Validation Method |
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| Conditions | hESCs (WA-09) |
| Disease | 80169.0 |
| Location of target site | 3'UTR |
| Tools used in this research | TargetScan , miRTarCLIP , Piranha |
| Original Description (Extracted from the article) |
...
"PAR-CLIP data was present in SRR359787. RNA binding protein: AGO2. Condition:4-thiouridine
... - Lipchina I; Elkabetz Y; Hafner M; Sheridan et al., 2011, Genes & development. |
| Article |
- Lipchina I; Elkabetz Y; Hafner M; Sheridan et al. - Genes & development, 2011
MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due to the lack of genome-wide strategies to identify their targets. Here, we performed comprehensive microRNA profiling in hESCs and in purified neural and mesenchymal derivatives. Using a combination of AGO cross-linking and microRNA perturbation experiments, together with computational prediction, we identified the targets of the miR-302/367 cluster, the most abundant microRNAs in hESCs. Functional studies identified novel roles of miR-302/367 in maintaining pluripotency and regulating hESC differentiation. We show that in addition to its role in TGF-beta signaling, miR-302/367 promotes bone morphogenetic protein (BMP) signaling by targeting BMP inhibitors TOB2, DAZAP2, and SLAIN1. This study broadens our understanding of microRNA function in hESCs and is a valuable resource for future studies in this area.
LinkOut: [PMID: 22012620]
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| Experimental Support 4 for Functional miRNA-Target Interaction | |||||||
|---|---|---|---|---|---|---|---|
| miRNA:Target | ---- | ||||||
| Validation Method |
|
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| Conditions | HEK293 | ||||||
| Disease | 80169.0 | ||||||
| Location of target site | 3'UTR | ||||||
| Tools used in this research | TargetScan , miRTarCLIP , Piranha | ||||||
| Original Description (Extracted from the article) |
...
"PAR-CLIP data was present in GSM1065667. RNA binding protein: AGO1. Condition:4-thiouridine
"PAR-CLIP data was present in GSM1065668. RNA binding protein: AGO1. Condition:4-thiouridine
"PAR-CLIP data was present in GSM1065670. RNA binding protein: AGO2. Condition:4-thiouridine
... - Memczak S; Jens M; Elefsinioti A; Torti F; et al., 2013, Nature. |
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| miRNA-target interactions (Provided by authors) |
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| Article |
- Memczak S; Jens M; Elefsinioti A; Torti F; et al. - Nature, 2013
Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.
LinkOut: [PMID: 23446348]
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| Experimental Support 5 for Functional miRNA-Target Interaction | |
|---|---|
| miRNA:Target | ---- |
| Validation Method |
|
| Conditions | HEK293/HeLa |
| Location of target site | 3'UTR |
| Tools used in this research | TargetScan , miRTarCLIP , Piranha |
| Original Description (Extracted from the article) |
...
HITS-CLIP data was present in GSM1067869. RNA binding protein: AGO2. Condition:Ago2 IP-seq (asynchronous cells)
HITS-CLIP data was present in GSM1067870. RNA binding protein: AGO2. Condition:Ago2 IP-seq (mitotic cells)
... - Kishore S; Gruber AR; Jedlinski DJ; Syed et al., 2013, Genome biology. |
| Article |
- Kishore S; Gruber AR; Jedlinski DJ; Syed et al. - Genome biology, 2013
BACKGROUND: In recent years, a variety of small RNAs derived from other RNAs with well-known functions such as tRNAs and snoRNAs, have been identified. The functional relevance of these RNAs is largely unknown. To gain insight into the complexity of snoRNA processing and the functional relevance of snoRNA-derived small RNAs, we sequence long and short RNAs, small RNAs that co-precipitate with the Argonaute 2 protein and RNA fragments obtained in photoreactive nucleotide-enhanced crosslinking and immunoprecipitation (PAR-CLIP) of core snoRNA-associated proteins. RESULTS: Analysis of these data sets reveals that many loci in the human genome reproducibly give rise to C/D box-like snoRNAs, whose expression and evolutionary conservation are typically less pronounced relative to the snoRNAs that are currently cataloged. We further find that virtually all C/D box snoRNAs are specifically processed inside the regions of terminal complementarity, retaining in the mature form only 4-5 nucleotides upstream of the C box and 2-5 nucleotides downstream of the D box. Sequencing of the total and Argonaute 2-associated populations of small RNAs reveals that despite their cellular abundance, C/D box-derived small RNAs are not efficiently incorporated into the Ago2 protein. CONCLUSIONS: We conclude that the human genome encodes a large number of snoRNAs that are processed along the canonical pathway and expressed at relatively low levels. Generation of snoRNA-derived processing products with alternative, particularly miRNA-like, functions appears to be uncommon.
LinkOut: [PMID: 23706177]
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| Experimental Support 6 for Functional miRNA-Target Interaction | |
|---|---|
| miRNA:Target | ---- |
| Validation Method |
|
| Conditions | MCF7 |
| Location of target site | 3'UTR |
| Tools used in this research | TargetScan , miRTarCLIP , Piranha |
| Original Description (Extracted from the article) |
...
PAR-CLIP data was present in SRR1045082. RNA binding protein: AGO2. Condition:Untreated
... - Farazi TA; Ten Hoeve JJ; Brown M; et al., 2014, Genome biology. |
| Article |
- Farazi TA; Ten Hoeve JJ; Brown M; et al. - Genome biology, 2014
BACKGROUND: Various microRNAs (miRNAs) are up- or downregulated in tumors. However, the repression of cognate miRNA targets responsible for the phenotypic effects of this dysregulation in patients remains largely unexplored. To define miRNA targets and associated pathways, together with their relationship to outcome in breast cancer, we integrated patient-paired miRNA-mRNA expression data with a set of validated miRNA targets and pathway inference. RESULTS: To generate a biochemically-validated set of miRNA-binding sites, we performed argonaute-2 photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (AGO2-PAR-CLIP) in MCF7 cells. We then defined putative miRNA-target interactions using a computational model, which ranked and selected additional TargetScan-predicted interactions based on features of our AGO2-PAR-CLIP binding-site data. We subselected modeled interactions according to the abundance of their constituent miRNA and mRNA transcripts in tumors, and we took advantage of the variability of miRNA expression within molecular subtypes to detect miRNA repression. Interestingly, our data suggest that miRNA families control subtype-specific pathways; for example, miR-17, miR-19a, miR-25, and miR-200b show high miRNA regulatory activity in the triple-negative, basal-like subtype, whereas miR-22 and miR-24 do so in the HER2 subtype. An independent dataset validated our findings for miR-17 and miR-25, and showed a correlation between the expression levels of miR-182 targets and overall patient survival. Pathway analysis associated miR-17, miR-19a, and miR-200b with leukocyte transendothelial migration. CONCLUSIONS: We combined PAR-CLIP data with patient expression data to predict regulatory miRNAs, revealing potential therapeutic targets and prognostic markers in breast cancer.
LinkOut: [PMID: 24398324]
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| Experimental Support 7 for Functional miRNA-Target Interaction | |
|---|---|
| miRNA:Target | ---- |
| Validation Method |
|
| Conditions | HCT116 |
| Location of target site | 3'UTR |
| Tools used in this research | TargetScan , miRTarCLIP , Piranha |
| Original Description (Extracted from the article) |
...
PAR-CLIP data was present in ERX177606. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_2_8
PAR-CLIP data was present in ERX177616. RNA binding protein: AGO2. Condition:p53_V_AGO_CLIP_3_6
PAR-CLIP data was present in ERX177618. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_3_8
PAR-CLIP data was present in ERX177620. RNA binding protein: AGO2. Condition:p53_V_AGO_CLIP_3_10
PAR-CLIP data was present in ERX177604. RNA binding protein: AGO2. Condition:p53_V_AGO_CLIP_2_6
PAR-CLIP data was present in ERX177628. RNA binding protein: AGO2. Condition:p53_V_AGO_CLIP_4_6
PAR-CLIP data was present in ERX177608. RNA binding protein: AGO2. Condition:p53_V_AGO_CLIP_2_10
PAR-CLIP data was present in ERX177632. RNA binding protein: AGO2. Condition:p53_V_AGO_CLIP_4_10
PAR-CLIP data was present in ERX177624. RNA binding protein: AGO2. Condition:p53_V_AGO_CLIP_4_2
PAR-CLIP data was present in ERX177630. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_4_8
PAR-CLIP data was present in ERX177634. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_4_12
PAR-CLIP data was present in ERX177607. RNA binding protein: AGO2. Condition:p53_D_AGO_CLIP_2_9
PAR-CLIP data was present in ERX177619. RNA binding protein: AGO2. Condition:p53_D_AGO_CLIP_3_9
PAR-CLIP data was present in ERX177631. RNA binding protein: AGO2. Condition:p53_D_AGO_CLIP_4_9
PAR-CLIP data was present in ERX177611. RNA binding protein: AGO2. Condition:p53_D_AGO_CLIP_3_1
PAR-CLIP data was present in ERX177623. RNA binding protein: AGO2. Condition:p53_D_AGO_CLIP_4_1
PAR-CLIP data was present in ERX177605. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_2_7
PAR-CLIP data was present in ERX177614. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_3_4
PAR-CLIP data was present in ERX177621. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_3_11
PAR-CLIP data was present in ERX177629. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_4_7
PAR-CLIP data was present in ERX177622. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_3_12
PAR-CLIP data was present in ERX177601. RNA binding protein: AGO2. Condition:KO_D_Ago_CLIP_2_3
PAR-CLIP data was present in ERX177625. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_4_3
PAR-CLIP data was present in ERX177627. RNA binding protein: AGO2. Condition:p53_D_AGO_CLIP_4_5
PAR-CLIP data was present in ERX177609. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_2_11
PAR-CLIP data was present in ERX177602. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_2_4
PAR-CLIP data was present in ERX177603. RNA binding protein: AGO2. Condition:p53_D_AGO_CLIP_2_5
PAR-CLIP data was present in ERX177610. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_2_12
PAR-CLIP data was present in ERX177613. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_3_3
PAR-CLIP data was present in ERX177615. RNA binding protein: AGO2. Condition:p53_D_AGO_CLIP_3_5
PAR-CLIP data was present in ERX177617. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_3_7
PAR-CLIP data was present in ERX177626. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_4_4
PAR-CLIP data was present in ERX177633. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_4_11
PAR-CLIP data was present in ERX177599. RNA binding protein: AGO2. Condition:p53_D_AGO_CLIP_2_1
... - Krell J; Stebbing J; Carissimi C; Dabrowska et al., 2016, Genome research. |
| Article |
- Krell J; Stebbing J; Carissimi C; Dabrowska et al. - Genome research, 2016
DNA damage activates TP53-regulated surveillance mechanisms that are crucial in suppressing tumorigenesis. TP53 orchestrates these responses directly by transcriptionally modulating genes, including microRNAs (miRNAs), and by regulating miRNA biogenesis through interacting with the DROSHA complex. However, whether the association between miRNAs and AGO2 is regulated following DNA damage is not yet known. Here, we show that, following DNA damage, TP53 interacts with AGO2 to induce or reduce AGO2's association of a subset of miRNAs, including multiple let-7 family members. Furthermore, we show that specific mutations in TP53 decrease rather than increase the association of let-7 family miRNAs, reducing their activity without preventing TP53 from interacting with AGO2. This is consistent with the oncogenic properties of these mutants. Using AGO2 RIP-seq and PAR-CLIP-seq, we show that the DNA damage-induced increase in binding of let-7 family members to the RISC complex is functional. We unambiguously determine the global miRNA-mRNA interaction networks involved in the DNA damage response, validating them through the identification of miRNA-target chimeras formed by endogenous ligation reactions. We find that the target complementary region of the let-7 seed tends to have highly fixed positions and more variable ones. Additionally, we observe that miRNAs, whose cellular abundance or differential association with AGO2 is regulated by TP53, are involved in an intricate network of regulatory feedback and feedforward circuits. TP53-mediated regulation of AGO2-miRNA interaction represents a new mechanism of miRNA regulation in carcinogenesis.
LinkOut: [PMID: 26701625]
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| Experimental Support 8 for Functional miRNA-Target Interaction | |
|---|---|
| miRNA:Target | ---- |
| Validation Method |
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| Conditions | Prostate Tissue |
| Location of target site | 3'UTR |
| Tools used in this research | TargetScan , miRTarCLIP , Piranha |
| Original Description (Extracted from the article) |
...
PAR-CLIP data was present in SRX1760583. RNA binding protein: AGO2. Condition:AGO-CLIP-LNCaP_A
PAR-CLIP data was present in SRX1760638. RNA binding protein: AGO2. Condition:AGO-CLIP-PC3-miR148
PAR-CLIP data was present in SRX1760630. RNA binding protein: AGO2. Condition:AGO-CLIP-22RV1_A
PAR-CLIP data was present in SRX1760639. RNA binding protein: AGO2. Condition:AGO-CLIP-LNCaP-MDV_A
PAR-CLIP data was present in SRX1760641. RNA binding protein: AGO2. Condition:AGO-CLIP-LNCaP-MDV_B
PAR-CLIP data was present in SRX1760632. RNA binding protein: AGO2. Condition:AGO-CLIP-22RV1_C
... - Hamilton MP; Rajapakshe KI; Bader DA; Cerne et al., 2016, Neoplasia (New York, N.Y.). |
| Article |
- Hamilton MP; Rajapakshe KI; Bader DA; Cerne et al. - Neoplasia (New York, N.Y.), 2016
MicroRNA (miRNA) deregulation in prostate cancer (PCa) contributes to PCa initiation and metastatic progression. To comprehensively define the cancer-associated changes in miRNA targeting and function in commonly studied models of PCa, we performed photoactivatable ribonucleoside-enhanced cross-linking immunoprecipitation of the Argonaute protein in a panel of PCa cell lines modeling different stages of PCa progression. Using this comprehensive catalogue of miRNA targets, we analyzed miRNA targeting on known drivers of PCa and examined tissue-specific and stage-specific pathway targeting by miRNAs. We found that androgen receptor is the most frequently targeted PCa oncogene and that miR-148a targets the largest number of known PCa drivers. Globally, tissue-specific and stage-specific changes in miRNA targeting are driven by homeostatic response to active oncogenic pathways. Our findings indicate that, even in advanced PCa, the miRNA pool adapts to regulate continuing alterations in the cancer genome to balance oncogenic molecular changes. These findings are important because they are the first to globally characterize miRNA changes in PCa and demonstrate how the miRNA target spectrum responds to staged tumorigenesis.
LinkOut: [PMID: 27292025]
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| CLIP-seq Support 1 for dataset GSM714642 | |
|---|---|
| Method / RBP | HITS-CLIP / AGO2 |
| Cell line / Condition | HEK293 / completeT1, repA |
| Location of target site | ENST00000315684.8 | 3UTR | AAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUCAUAUUUU |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 21572407 / GSE28865 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 2 for dataset GSM1067869 | |
|---|---|
| Method / RBP | HITS-CLIP / AGO2 |
| Cell line / Condition | HEK293/HeLa / Ago2 IP-seq (asynchronous cells) |
| Location of target site | ENST00000315684.8 | 3UTR | AAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUC |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 23706177 / GSE43666 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 3 for dataset GSM1067870 | |
|---|---|
| Method / RBP | HITS-CLIP / AGO2 |
| Cell line / Condition | HEK293/HeLa / Ago2 IP-seq (mitotic cells) |
| Location of target site | ENST00000315684.8 | 3UTR | AAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUC |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 23706177 / GSE43666 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 4 for dataset GSM545212 | |
|---|---|
| Method / RBP | PAR-CLIP / AGO1 |
| Cell line / Condition | HEK293 / Control |
| Location of target site | ENST00000315684.8 | 3UTR | AAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUCAUAU |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 20371350 / GSE21578 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 5 for dataset GSM545215 | |
|---|---|
| Method / RBP | PAR-CLIP / AGO4 |
| Cell line / Condition | HEK293 / Control |
| Location of target site | ENST00000315684.8 | 3UTR | AGAAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUCAUAUUUU |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 20371350 / GSE21578 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 6 for dataset GSM545217 | |
|---|---|
| Method / RBP | PAR-CLIP / AGO2 |
| Cell line / Condition | HEK293 / miR-7 transfection |
| Location of target site | ENST00000315684.8 | 3UTR | AAGCCUCGUAGUCGUGGCCGAGUGGUUAAGGCGAUGGACUAGAAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUCAUA |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 20371350 / GSE21578 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 7 for dataset GSM714645 | |
|---|---|
| Method / RBP | PAR-CLIP / AGO2 |
| Cell line / Condition | HEK293 / completeT1, repB |
| Location of target site | ENST00000315684.8 | 3UTR | AAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUCAUAUUUU |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 21572407 / GSE28865 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 8 for dataset SRR359787 | |
|---|---|
| Method / RBP | PAR-CLIP / AGO2 |
| Cell line / Condition | hESCs (WA-09) / 4-thiouridine, RNase T1 |
| Location of target site | ENST00000315684.8 | 3UTR | AAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUCAUAUUUUUUU |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 22012620 / SRX103431 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 9 for dataset GSM1065667 | |
|---|---|
| Method / RBP | PAR-CLIP / AGO1 |
| Cell line / Condition | HEK293 / 4-thiouridine, ML_MM_6 |
| Location of target site | ENST00000315684.8 | 3UTR | AAGCCUCGUAGUCGUGGCCGAGUGGUUAAGGCGAUGGACUAGAAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUCAUAUUUU |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 23446348 / GSE43573 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 10 for dataset GSM1065668 | |
|---|---|
| Method / RBP | PAR-CLIP / AGO1 |
| Cell line / Condition | HEK293 / 4-thiouridine, ML_MM_7 |
| Location of target site | ENST00000315684.8 | 3UTR | AAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUCAUA |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 23446348 / GSE43573 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 11 for dataset GSM1065670 | |
|---|---|
| Method / RBP | PAR-CLIP / AGO2 |
| Cell line / Condition | HEK293 / 4-thiouridine, 3_ML_LG |
| Location of target site | ENST00000315684.8 | 3UTR | UUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUCAUAUUU |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 23446348 / GSE43573 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 12 for dataset SRR1045082 | |
|---|---|
| Method / RBP | PAR-CLIP / AGO2 |
| Cell line / Condition | MCF7 / Untreated |
| Location of target site | ENST00000315684.8 | 3UTR | AAAUCCAUUGGGGUCUCCCCGCGCAGGUUCGAAUCCUGCCGACUACGUCAU |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 24398324 / SRX388831 |
| CLIP-seq Viewer | Link |
| MiRNA-Target Expression Profile | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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| MiRNA-Target Expression Profile (TCGA) | |||||||
|---|---|---|---|---|---|---|---|
|
13 hsa-miR-1539 Target Genes:
Functional analysis:
ID |
Target | Description | Validation methods |
 |
 |
|||||||
| Strong evidence | Less strong evidence | |||||||||||
 |
 |
 |
 |
 |
 |
 |
 |
|||||
| MIRT447455 | IFNK | interferon kappa |  |
|
2 | 2 | ||||||
| MIRT467605 | SLC7A5 | solute carrier family 7 member 5 | |
|
2 | 2 | ||||||
| MIRT492748 | PER1 | period circadian clock 1 | |
|
2 | 10 | ||||||
| MIRT502664 | CTC1 | CST telomere replication complex component 1 | |
|
2 | 12 | ||||||
| MIRT526463 | OSBPL5 | oxysterol binding protein like 5 | |
|
2 | 2 | ||||||
| MIRT530649 | ETV5 | ETS variant 5 | |
|
2 | 2 | ||||||
| MIRT564511 | DUSP3 | dual specificity phosphatase 3 | |
|
2 | 2 | ||||||
| MIRT633714 | TNFAIP8L1 | TNF alpha induced protein 8 like 1 | |
|
2 | 2 | ||||||
| MIRT637371 | ORAI2 | ORAI calcium release-activated calcium modulator 2 | |
|
2 | 2 | ||||||
| MIRT678462 | GLYAT | glycine-N-acyltransferase | |
|
2 | 2 | ||||||
| MIRT689346 | ZNF83 | zinc finger protein 83 | |
|
2 | 2 | ||||||
| MIRT712905 | TGFA | transforming growth factor alpha | |
|
2 | 2 | ||||||
| MIRT717041 | KRTAP4-9 | keratin associated protein 4-9 | |
|
2 | 2 | ||||||
| miRNA-Drug Associations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| miRNA-Drug Resistance Associations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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