| pre-miRNA Information | |
|---|---|
| pre-miRNA | hsa-mir-3689e |
| Genomic Coordinates | chr9: 134850570 - 134850641 |
| Description | Homo sapiens miR-3689e stem-loop |
| Comment | None |
| RNA Secondary Structure |  |
| Mature miRNA Information | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mature miRNA | hsa-miR-3689e | ||||||||||||||||||||||||
| Sequence | 7| UGUGAUAUCAUGGUUCCUGGGA |28 | ||||||||||||||||||||||||
| Evidence | Experimental | ||||||||||||||||||||||||
| Experiments | Illumina | ||||||||||||||||||||||||
| SNPs in miRNA |
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| Putative Targets | |||||||||||||||||||||||||
| Gene Information | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene Symbol | INVS | ||||||||||||||||||||
| Synonyms | INV, NPH2, NPHP2 | ||||||||||||||||||||
| Description | inversin | ||||||||||||||||||||
| Transcript | NM_014425 | ||||||||||||||||||||
| Expression | |||||||||||||||||||||
| Putative miRNA Targets on INVS | |||||||||||||||||||||
| 3'UTR of INVS (miRNA target sites are highlighted) |
>INVS|NM_014425|3'UTR 1 CTGCCTATGGAGGAAGACTGTGTTCGGGGGAGCTGGCATAGCTAGTGCAGAGTTCAGATTTTCTGCTGATAATCTTTTAC 81 ACCTTGGGAAAACTTTAATATCCGTACCTGAAGGCTGATTCACCTAAAAATGTGTTAACTGAAAGAAAATGTCAGAATGT 161 TTCCTTTCTGCTCTTACACAGCATTGTTTTGTCAATCAACACAGCCTGCACTGAAAGGACCTGCATAGACTATGTCTGTG 241 CAAAGTGCCTGAGTGTCTGCTTTCACCTCAGTCTGTACAGTTGGAAATGAGAATTCATAATTAACAGCAAAATCTAAGGA 321 AAACTACGGCTGCTGGGTTGGGATTTCTGCCAGCTAGCTGGTACTGGCTTCTTGTTTCAAGAGATGAACCTAAATGAGAT 401 AGGAAGCCTGTCCCATAGCAGCCTTCCTCTCACTACTTTCCTGGCATCTAATGCAACAAACTTATCACACACACACACAC 481 ACACACACACACACACACACACACATATCACGTCCCACTATTACTTCAAAATTAATCAGGTTTAAATTTTAGATCAGAAT 561 CATTGCCCACTGTTTTCATTTAGAAATTGTCCAAAAGACCATAGATACATTCTGGTGATTCCTTACATTTTACAGTTCCT 641 ACGTTAGCCTCTCAAGGCCACAAGTTGCCGCCACGTCTTCACTGAATGGCTTTCTCAGTGCTGAATACCAACAGCCGTAT 721 TACAGTATCAAGGATTCTGTCAGGTAGGGTTTACAGACCAGACTGTTCATGCAGCAAGGTGCTAACTCAGGCGTCAACGT 801 TCTACTTGTATTTTCTGACCAACTTGCAGAAGTGAGCAATCTTCTTAAAATGCCATTTCTGTTGGCAGGGAAGAATGAAA 881 CGGCACACATCCTAGCATTCTAAGAACACCTGGTTTAAATAAAATCCAGTGATGATGGGCTCTTTCACATTGTTTAAGGG 961 GAAAGCTGCTGTGAGAATATTGACAGTAGGCATAAACAGTGATATATTTTACTCACAGGTATTTTGGGGGTTGCTTTCAT 1041 TTTCTTCAGATCAGTGCCACTTCTGTGCTAACGGTAAGAGATAGACAGATAGGCAATGAAGTGTTCACTTAATTACCTTG 1121 GTTTTTAGTTTACTAATTATTACATTCATCGTTTTTGTGATCACAAAAACACAAAGAAGGAGGTCTGCCTGGATGGAATT 1201 ACAAAGATTTAGCCAGTTTCTTGGTATATAACAGAAGGTACCACAGTATCACTCTCTATTTTGTAAATATTTAGCTCCTA 1281 TGAAATGCACAATGCACAACCGCCTATGACCATGTATCGTGTGCTAGTCCGGGAAGCCAGCCTACACATCAATAGGAACG 1361 CCCAAACATTATTTTCATATATCAGTGCAAAGAAAGAAGGTTCGTAAACTTCTTTAAAAGTTCAGCTTTAATGACAAAGA 1441 TCTATTACATCAGTCTTTTTCTTCAAATAAGATAGATGTGAATAAACAACTTCAAACAGGAAAAAAAAAAAAAAAAAAAA 1521 AAAAAA 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 | hESCs (WA-09) | ||||||
| Disease | 27130.0 | ||||||
| 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. |
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| miRNA-target interactions (Provided by authors) |
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| 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 2 for Functional miRNA-Target Interaction | |||||||
|---|---|---|---|---|---|---|---|
| miRNA:Target | ---- | ||||||
| Validation Method |
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| Conditions | 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 GSM1048188. RNA binding protein: AGO2. Condition:Hela_AGO2_CLIP_ptb_knockdown
... - Xue Y; Ouyang K; Huang J; Zhou Y; Ouyang H; et al., 2013, Cell. |
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| miRNA-target interactions (Provided by authors) |
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| Article |
- Xue Y; Ouyang K; Huang J; Zhou Y; Ouyang H; et al. - Cell, 2013
The induction of pluripotency or trans-differentiation of one cell type to another can be accomplished with cell-lineage-specific transcription factors. Here, we report that repression of a single RNA binding polypyrimidine-tract-binding (PTB) protein, which occurs during normal brain development via the action of miR-124, is sufficient to induce trans-differentiation of fibroblasts into functional neurons. Besides its traditional role in regulated splicing, we show that PTB has a previously undocumented function in the regulation of microRNA functions, suppressing or enhancing microRNA targeting by competitive binding on target mRNA or altering local RNA secondary structure. A key event during neuronal induction is the relief of PTB-mediated blockage of microRNA action on multiple components of the REST complex, thereby derepressing a large array of neuronal genes, including miR-124 and multiple neuronal-specific transcription factors, in nonneuronal cells. This converts a negative feedback loop to a positive one to elicit cellular reprogramming to the neuronal lineage.
LinkOut: [PMID: 23313552]
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| Experimental Support 3 for Functional miRNA-Target Interaction | |
|---|---|
| miRNA:Target | ---- |
| Validation Method |
|
| Conditions | HEK293S |
| 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 GSM1084064. RNA binding protein: AGO2. Condition:CLIP_noemetine_AbnovaAb
... - Karginov FV; Hannon GJ, 2013, Genes & development. |
| Article |
- Karginov FV; Hannon GJ - Genes & development, 2013
When adapting to environmental stress, cells attenuate and reprogram their translational output. In part, these altered translation profiles are established through changes in the interactions between RNA-binding proteins and mRNAs. The Argonaute 2 (Ago2)/microRNA (miRNA) machinery has been shown to participate in stress-induced translational up-regulation of a particular mRNA, CAT-1; however, a detailed, transcriptome-wide understanding of the involvement of Ago2 in the process has been lacking. Here, we profiled the overall changes in Ago2-mRNA interactions upon arsenite stress by cross-linking immunoprecipitation (CLIP) followed by high-throughput sequencing (CLIP-seq). Ago2 displayed a significant remodeling of its transcript occupancy, with the majority of 3' untranslated region (UTR) and coding sequence (CDS) sites exhibiting stronger interaction. Interestingly, target sites that were destined for release from Ago2 upon stress were depleted in miRNA complementarity signatures, suggesting an alternative mode of interaction. To compare the changes in Ago2-binding patterns across transcripts with changes in their translational states, we measured mRNA profiles on ribosome/polysome gradients by RNA sequencing (RNA-seq). Increased Ago2 occupancy correlated with stronger repression of translation for those mRNAs, as evidenced by a shift toward lighter gradient fractions upon stress, while release of Ago2 was associated with the limited number of transcripts that remained translated. Taken together, these data point to a role for Ago2 and the mammalian miRNAs in mediating the translational component of the stress response.
LinkOut: [PMID: 23824327]
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| Experimental Support 4 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) |
...
HITS-CLIP data was present in GSM1395164. RNA binding protein: AGO. Condition:MCF7 AGO HITS-CLIP Replicate 2
... - Pillai MM; Gillen AE; Yamamoto TM; Kline E; et al., 2014, Breast cancer research and treatment. |
| Article |
- Pillai MM; Gillen AE; Yamamoto TM; Kline E; et al. - Breast cancer research and treatment, 2014
miRNAs regulate the expression of genes in both normal physiology and disease. While miRNAs have been demonstrated to play a pivotal role in aspects of cancer biology, these reports have generally focused on the regulation of single genes. Such single-gene approaches have significant limitations, relying on miRNA expression levels and heuristic predictions of mRNA-binding sites. This results in only circumstantial evidence of miRNA-target interaction and typically leads to large numbers of false positive predictions. Here, we used a genome-wide approach (high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation, HITS-CLIP) to define direct miRNA-mRNA interactions in three breast cancer subtypes (estrogen receptor positive, Her2 amplified, and triple negative). Focusing on steroid receptor signaling, we identified two novel regulators of the ER pathway (miR-9-5p and miR-193a/b-3p), which together target multiple genes involved in ER signaling. Moreover, this approach enabled the definition of miR-9-5p as a global regulator of steroid receptor signaling in breast cancer. We show that miRNA targets and networks defined by HITS-CLIP under physiologic conditions are predictive of patient outcomes and provide global insight into miRNA regulation in breast cancer.
LinkOut: [PMID: 24906430]
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| Experimental Support 5 for Functional miRNA-Target Interaction | |
|---|---|
| miRNA:Target | ---- |
| Validation Method |
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| Conditions | Cardiac Tissues |
| 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 GSM2202481. RNA binding protein: AGO2. Condition:S6_LV_61yo_Male_AGO2_bound_RNA
HITS-CLIP data was present in GSM2202477. RNA binding protein: AGO2. Condition:S2_LV_25yo_Male_AGO2_bound_RNA
HITS-CLIP data was present in GSM2202478. RNA binding protein: AGO2. Condition:S3_LV_36yo_Male_AGO2_bound_RNA
HITS-CLIP data was present in GSM2202476. RNA binding protein: AGO2. Condition:S1_LV_54yo_Male_AGO2_bound_RNA
... - Spengler RM; Zhang X; Cheng C; McLendon JM; et al., 2016, Nucleic acids research. |
| Article |
Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP.
- Spengler RM; Zhang X; Cheng C; McLendon JM; et al.- Nucleic acids research, 2016
MicroRNAs (miRs) have emerged as key biological effectors in human health and disease. These small noncoding RNAs are incorporated into Argonaute (Ago) proteins, where they direct post-transcriptional gene silencing via base-pairing with target transcripts. Although miRs have become intriguing biological entities and attractive therapeutic targets, the translational impacts of miR research remain limited by a paucity of empirical miR targeting data, particularly in human primary tissues. Here, to improve our understanding of the diverse roles miRs play in cardiovascular function and disease, we applied high-throughput methods to globally profile miR:target interactions in human heart tissues. We deciphered Ago2:RNA interactions using crosslinking immunoprecipitation coupled with high-throughput sequencing (HITS-CLIP) to generate the first transcriptome-wide map of miR targeting events in human myocardium, detecting 4000 cardiac Ago2 binding sites across >2200 target transcripts. Our initial exploration of this interactome revealed an abundance of miR target sites in gene coding regions, including several sites pointing to new miR-29 functions in regulating cardiomyocyte calcium, growth and metabolism. Also, we uncovered several clinically-relevant interactions involving common genetic variants that alter miR targeting events in cardiomyopathy-associated genes. Overall, these data provide a critical resource for bolstering translational miR research in heart, and likely beyond.
LinkOut: [PMID: 27418678]
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| CLIP-seq Support 1 for dataset GSM1048188 | |
|---|---|
| Method / RBP | HITS-CLIP / AGO2 |
| Cell line / Condition | Hela / Hela_AGO2_CLIP_ptb_knockdown |
| Location of target site | ENST00000262457.2 | 3UTR | ACACACACACACACACACACACAUAUCAC |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 23313552 / GSE42701 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 2 for dataset GSM1084064 | |
|---|---|
| Method / RBP | HITS-CLIP / AGO2 |
| Cell line / Condition | HEK293S / CLIP_noemetine_AbnovaAb |
| Location of target site | ENST00000262457.2 | 3UTR | UUAUCACACACACACACACACAC |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 23824327 / GSE44404 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 3 for dataset GSM1395164 | |
|---|---|
| Method / RBP | HITS-CLIP / AGO |
| Cell line / Condition | MCF7 / MCF7 AGO HITS-CLIP Replicate 2 |
| Location of target site | ENST00000262457.2 | 3UTR | UAUCACACACACACACACACACACACACACACACA |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 24906430 / GSE57855 |
| CLIP-seq Viewer | Link |
| CLIP-seq Support 4 for dataset SRR359787 | |
|---|---|
| Method / RBP | PAR-CLIP / AGO2 |
| Cell line / Condition | hESCs (WA-09) / 4-thiouridine, RNase T1 |
| Location of target site | ENST00000262457.2 | 3UTR | CACACACACACACACACAUAUCACG |
| Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
| Article / Accession Series | PMID: 22012620 / SRX103431 |
| CLIP-seq Viewer | Link |
| MiRNA-Target Expression Profile | |||||||
|---|---|---|---|---|---|---|---|
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| MiRNA-Target Expression Profile (TCGA) | |||||||
|---|---|---|---|---|---|---|---|
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45 hsa-miR-3689e Target Genes:
Functional analysis:
ID |
Target | Description | Validation methods |
 |
 |
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| Strong evidence | Less strong evidence | |||||||||||
 |
 |
 |
 |
 |
 |
 |
 |
|||||
| MIRT112233 | MDM4 | MDM4, p53 regulator |  |
|
2 | 2 | ||||||
| MIRT188658 | FAM76A | family with sequence similarity 76 member A | |
|
2 | 2 | ||||||
| MIRT200913 | ZNF264 | zinc finger protein 264 | |
|
2 | 4 | ||||||
| MIRT210597 | KBTBD8 | kelch repeat and BTB domain containing 8 | |
|
2 | 6 | ||||||
| MIRT299209 | CSRNP3 | cysteine and serine rich nuclear protein 3 | |
|
2 | 2 | ||||||
| MIRT317526 | SLC39A7 | solute carrier family 39 member 7 | |
|
2 | 2 | ||||||
| MIRT355852 | SGMS2 | sphingomyelin synthase 2 | |
|
2 | 4 | ||||||
| MIRT443050 | THRB | thyroid hormone receptor beta | |
|
2 | 2 | ||||||
| MIRT446629 | SDC3 | syndecan 3 | |
|
2 | 2 | ||||||
| MIRT449407 | TRIM5 | tripartite motif containing 5 | |
|
2 | 2 | ||||||
| MIRT463559 | ZBTB39 | zinc finger and BTB domain containing 39 | |
|
2 | 6 | ||||||
| MIRT465701 | TNFAIP1 | TNF alpha induced protein 1 | |
|
2 | 2 | ||||||
| MIRT472686 | MYCBP | MYC binding protein | |
|
2 | 4 | ||||||
| MIRT493285 | LNPEP | leucyl and cystinyl aminopeptidase | |
|
2 | 2 | ||||||
| MIRT499336 | RAB25 | RAB25, member RAS oncogene family | |
|
2 | 2 | ||||||
| MIRT501721 | OVOL1 | ovo like transcriptional repressor 1 | |
|
2 | 2 | ||||||
| MIRT507975 | BCL2L13 | BCL2 like 13 | |
|
2 | 4 | ||||||
| MIRT511809 | HDGF | heparin binding growth factor | |
|
2 | 6 | ||||||
| MIRT516709 | PIK3CG | phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma | |
|
2 | 4 | ||||||
| MIRT527851 | SMOC1 | SPARC related modular calcium binding 1 | |
|
2 | 2 | ||||||
| MIRT531284 | SLC7A7 | solute carrier family 7 member 7 | |
|
2 | 2 | ||||||
| MIRT531892 | INVS | inversin | |
|
2 | 8 | ||||||
| MIRT536805 | HNRNPA1 | heterogeneous nuclear ribonucleoprotein A1 | |
|
2 | 2 | ||||||
| MIRT537805 | EFNB2 | ephrin B2 | |
|
2 | 4 | ||||||
| MIRT544333 | LPGAT1 | lysophosphatidylglycerol acyltransferase 1 | |
|
2 | 2 | ||||||
| MIRT547140 | PGM3 | phosphoglucomutase 3 | |
|
2 | 2 | ||||||
| MIRT547427 | MED4 | mediator complex subunit 4 | |
|
2 | 2 | ||||||
| MIRT563352 | ZNF181 | zinc finger protein 181 | |
|
2 | 2 | ||||||
| MIRT564847 | ZBED3 | zinc finger BED-type containing 3 | |
|
2 | 2 | ||||||
| MIRT566424 | PIGA | phosphatidylinositol glycan anchor biosynthesis class A | |
|
2 | 2 | ||||||
| MIRT572510 | KIAA0232 | KIAA0232 | |
|
2 | 2 | ||||||
| MIRT574680 | HNRNPA3 | heterogeneous nuclear ribonucleoprotein A3 | |
|
2 | 2 | ||||||
| MIRT608818 | ONECUT3 | one cut homeobox 3 | |
|
2 | 6 | ||||||
| MIRT608884 | CLIC6 | chloride intracellular channel 6 | |
|
2 | 2 | ||||||
| MIRT608957 | GIMAP1 | GTPase, IMAP family member 1 | |
|
2 | 4 | ||||||
| MIRT609010 | HPS3 | HPS3, biogenesis of lysosomal organelles complex 2 subunit 1 | |
|
2 | 2 | ||||||
| MIRT641429 | SCUBE3 | signal peptide, CUB domain and EGF like domain containing 3 | |
|
2 | 2 | ||||||
| MIRT661839 | ZNF587B | zinc finger protein 587B | |
|
2 | 2 | ||||||
| MIRT690649 | RPF2 | ribosome production factor 2 homolog | |
|
2 | 2 | ||||||
| MIRT704617 | CLIP1 | CAP-Gly domain containing linker protein 1 | |
|
2 | 2 | ||||||
| MIRT708712 | PTPLAD2 | 3-hydroxyacyl-CoA dehydratase 4 | |
1 | 1 | |||||||
| MIRT710661 | CSTF2T | cleavage stimulation factor subunit 2 tau variant | |
|
2 | 2 | ||||||
| MIRT711258 | TPCN2 | two pore segment channel 2 | |
|
2 | 2 | ||||||
| MIRT714647 | FSTL1 | follistatin like 1 | |
|
2 | 2 | ||||||
| MIRT718516 | COL19A1 | collagen type XIX alpha 1 chain | |
|
2 | 2 | ||||||