pre-miRNA Information
pre-miRNA mmu-mir-186   
Genomic Coordinates chr3: 157544279 - 157544349
Synonyms Mirn186, mmu-mir-186, Mir186
Description Mus musculus miR-186 stem-loop
Comment The mature sequence shown here represents the most commonly cloned form from large-scale cloning studies .
RNA Secondary Structure

Mature miRNA Information
Mature miRNA mmu-miR-186-5p
Sequence 7| CAAAGAAUUCUCCUUUUGGGCU |28
Evidence Experimental
Experiments Cloned
Putative Targets

Gene Information
Gene Symbol Mmp12   
Synonyms AV378681, MME, Mmel
Description matrix metallopeptidase 12
Transcript NM_008605   
Expression
Putative miRNA Targets on Mmp12
3'UTR of Mmp12
(miRNA target sites are highlighted)
>Mmp12|NM_008605|3'UTR
   1 GAAGAATGTAGTGAAGGGTGCTTGCTGGTTTTTCAGTTTTATAAGTATATTTATTACATATTCACTCTATGCTCAGGGTG
  81 TAACTATGTGGCAATAATGTAACAGGAAATAAGGGGAGGTGTACAGGTCACACACACATAGTTACACAGAAAAGTGCTTT
 161 TACAAAATTAACCTCTTTTAGGAAACTTTTTTCACTTCATTCTATTCTTAATTTTGAAAGTGCATGGTTCAGAGGCCAAC
 241 TGGTTTATCTGTAAGTTGTTTTCTAACAACCTTCAAGTAGAAATATTAGAATTACTCTCTTGTCTTTACTGAAATGTAAC
 321 ATGTTTTGTTTTCTTTAAATAAATTGAAAGAAAGTGTTTGCCTTTTAATTTTTTCTTTAAAAAAGTGTGTGTGTGTGTGT
 401 GTGTGTGTGTGTGTATGTTGCCTATGTGCATATTTATGTACCACCTGCTGGTAGAAGACAGAAGAGGATGTCAGGTCCCT
 481 AGAAACAGGAGTTATCATGGTTATGGGAAACATTGTGGGTGCTGGGGATTGAATTCATATCTCCTAAAAGAGCAGCCTGT
 561 GCTCTTTGCTCCTGTGTCATCTCTCCAGCCCCAGTTATAATATTTTTCTTGAAAAGTCAATCAATTTTGAAAATAACTGT
 641 GGTCTTCTAAATAAAATCTTTCTGTGACTGTACCAAGCCATCAATGGAGATGTGATAGCTATAAGAAGTTGAAGCTTGGA
 721 GTCCTTTTAATCACTTGTGTATGAACAGCAGTCTAAACCCAAGACAAGAAAGCATTCTCTAGCCAGCACATGACTCCAAA
 801 GGTAGCTCCATATGACCACAAGACTGAAGAGGAGGTAGGAGGAAATAAGGCTTCTGTTCTTGTTAGATGTGTTGTGTGGC
 881 TCATTTCACATCAGAAAGTGGGTTGTAGCATTGCTATGTGGCCTTACAGGACATTAAATGGAAGCCTCCTTAAGCACAGG
 961 AGGAACTATGAGTAGCACACGCTTTGTTTGTCACAGGAAAAAGACAACATGGTGAGCCTGCCATGTCTGTGTCCTGGTCT
1041 GCCTTCTATCAGTTTTATTTTCTGTCCTGACATCTTGGCTCCCTATCTTCTGTATTGTGTATGCTGTAGAGATCTCAAAG
1121 CTTGTGAGTTTGTGAAGTATGTCCAATGTTAAAACTGACTGGTGTATTGTCCAAGAAACAGAGAACCCTTCATAGCAGAT
1201 TGTCATTCAGGCATTTTTGGAGACTGAAATGAACTGAAATAGGAATGACATGAGGAAAGGGCTCCTTTGCTCCATGTGTC
1281 AGATGTGAGTATTAACCTTCGACATCAACTTCATGAGATCCAGAGTCATGTAAGAGACATGTGAGCACTACTTCAAAGAA
1361 GGTAAATGGTAGGGAGCATTGTCACTCTCAGAGCAGGTGGCAGATCGATGACAGTCCCATCATGGGAAGGACAGCATTTT
1441 GTCCTTAATAGGATAGGTCATTAATTTTGGTTATGAATTTGCATTTCCTGTACATAGTGCTCCTGCTCAAACTATCACCC
1521 ATGGACTTACAGCATACCTTACCACCACCATAGTATTCCACACAACATTGTTTCTGTTCAGGGACCTCATTTCACAGCCA
1601 CAGTAGAGTCACATTAGGCTCACATTCATGTTGATATTCATGCTCTGCACAGTCCTGACACGGGAAAAACATCTGCTTTA
1681 TAGACTGCTGTAAGCCTTTGATTGATTTCTAGAATCTTTATCTTCTCAGTATTAGAGACTGAACCCAGGGCCGTGTGTGT
1761 ACAACAAAGCACGTGACCTTTAAGTTATGTCCTAGCAGTTAAGATTCTGAAAAGGTCATTTTTTCTGCTATTTTTATGCT
1841 GGTGTTTTTGTTACTTTTATGAAAAAAAATATTTGGATTACCCTTTATTTAATCATTCCAGGTGGCATGGCTTTTAGATT
1921 ATTAATTTTAGTGTTGACAGCAAACAGATATTTAAAGCCTTAAATTAATGCTACTATTCTCATAATAATTCTGTCAGCGT
2001 GGATTTTTTCAGGAAATGTATTATTTATATTAAAGTGTTATTTAGCTGACTCAATACCTAAAATATTTTCATAACTTCTG
2081 CTATGGCAAATGTTTCCTGAGACAGAATAACAAATAAAAACTCTTCAAAATCTG
Target sites Provided by authors   Predicted by miRanda    DRVs    SNPs    DRVs & SNPs
miRNA-target interactions
(Predicted by miRanda)
ID Duplex structure Position Score MFE
1
miRNA  3' ucGGGUUUUCCUCUUAAGAAAc 5'
            :|::||| |:  |||:||| 
Target 5' atTCTGAAAAGGTCATTTTTTc 3'
1804 - 1825 144.00 -9.20
2
miRNA  3' ucGGGUUUUC-CUCUUAAGAAAc 5'
            :|::  || | |:|||:||| 
Target 5' atTCTGTCAGCGTGGATTTTTTc 3'
1988 - 2010 136.00 -5.50
3
miRNA  3' ucGGGUUUUCCUCU----UAAGAAAc 5'
            |||||:|  |||    ||||| | 
Target 5' aaCCCAAGACAAGAAAGCATTCTCTa 3'
756 - 781 134.00 -11.32
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target ----
Validation Method
     
Conditions Brain (Mouse neocortex)
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 Chi_BrainA_130_50. RNA binding protein: AGO. Condition:Brain A 2A8 P13 130 KD ...

- Chi SW; Zang JB; Mele A; Darnell RB, 2009, Nature.

Article - Chi SW; Zang JB; Mele A; Darnell RB
- Nature, 2009
MicroRNAs (miRNAs) have critical roles in the regulation of gene expression; however, as miRNA activity requires base pairing with only 6-8 nucleotides of messenger RNA, predicting target mRNAs is a major challenge. Recently, high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) has identified functional protein-RNA interaction sites. Here we use HITS-CLIP to covalently crosslink native argonaute (Ago, also called Eif2c) protein-RNA complexes in mouse brain. This produced two simultaneous data sets-Ago-miRNA and Ago-mRNA binding sites-that were combined with bioinformatic analysis to identify interaction sites between miRNA and target mRNA. We validated genome-wide interaction maps for miR-124, and generated additional maps for the 20 most abundant miRNAs present in P13 mouse brain. Ago HITS-CLIP provides a general platform for exploring the specificity and range of miRNA action in vivo, and identifies precise sequences for targeting clinically relevant miRNA-mRNA interactions.
LinkOut: [PMID: 19536157]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target ----
Validation Method
     
Conditions mESCs
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 GSM622570. RNA binding protein: AGO2. Condition:WT1A HITS-CLIP data was present in GSM622571. RNA binding protein: AGO2. Condition:WT1B HITS-CLIP data was present in GSM622572. RNA binding protein: AGO2. Condition:WT2 HITS-CLIP data was present in GSM622573. RNA binding protein: AGO2. Condition:KO1 HITS-CLIP data was present in GSM622574. RNA binding protein: AGO2. Condition:KO2 ...

- Leung AK; Young AG; Bhutkar A; Zheng GX; et al., 2011, Nature structural & molecular biology.

Article - Leung AK; Young AG; Bhutkar A; Zheng GX; et al.
- Nature structural & molecular biology, 2011
MicroRNAs (miRNAs) are 19-22-nucleotide noncoding RNAs that post-transcriptionally regulate mRNA targets. We have identified endogenous miRNA binding sites in mouse embryonic stem cells (mESCs), by performing photo-cross-linking immunoprecipitation using antibodies to Argonaute (Ago2) followed by deep sequencing of RNAs (CLIP-seq). We also performed CLIP-seq in Dicer(-)/(-) mESCs that lack mature miRNAs, allowing us to define whether the association of Ago2 with the identified sites was miRNA dependent. A significantly enriched motif, GCACUU, was identified only in wild-type mESCs in 3' untranslated and coding regions. This motif matches the seed of a miRNA family that constitutes ~68% of the mESC miRNA population. Unexpectedly, a G-rich motif was enriched in sequences cross-linked to Ago2 in both the presence and absence of miRNAs. Expression analysis and reporter assays confirmed that the seed-related motif confers miRNA-directed regulation on host mRNAs and that the G-rich motif can modulate this regulation.
LinkOut: [PMID: 21258322]
Experimental Support 3 for Functional miRNA-Target Interaction
miRNA:Target ----
Validation Method
     
Conditions CD4+ T cells (C57BL/6)
Disease MIMAT0000215
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 GSM1013576. RNA binding protein: AGO2. Condition:CD4+ T cells "HITS-CLIP data was present in GSM1013577. RNA binding protein: AGO2. Condition:CD4+ T cells "HITS-CLIP data was present in GSM1013579. RNA binding protein: AGO2. Condition:CD4+ T cells "HITS-CLIP data was present in GSM1013595. RNA binding protein: AGO2. Condition:CD4+ T cells ...

- Loeb GB; Khan AA; Canner D; Hiatt JB; et al., 2012, Molecular cell.

Article - Loeb GB; Khan AA; Canner D; Hiatt JB; et al.
- Molecular cell, 2012
MicroRNAs (miRNAs) are essential components of gene regulation, but identification of miRNA targets remains a major challenge. Most target prediction and discovery relies on perfect complementarity of the miRNA seed to the 3' untranslated region (UTR). However, it is unclear to what extent miRNAs target sites without seed matches. Here, we performed a transcriptome-wide identification of the endogenous targets of a single miRNA-miR-155-in a genetically controlled manner. We found that approximately 40% of miR-155-dependent Argonaute binding occurs at sites without perfect seed matches. The majority of these noncanonical sites feature extensive complementarity to the miRNA seed with one mismatch. These noncanonical sites confer regulation of gene expression, albeit less potently than canonical sites. Thus, noncanonical miRNA binding sites are widespread, often contain seed-like motifs, and can regulate gene expression, generating a continuum of targeting and regulation.
LinkOut: [PMID: 23142080]
Experimental Support 4 for Functional miRNA-Target Interaction
miRNA:Target ----
Validation Method
     
Conditions Liver
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 ERR266287. RNA binding protein: AGO2. Condition:B_Liver partial hapatectomy 36h HITS-CLIP data was present in ERR266292. RNA binding protein: AGO2. Condition:B_Liver partial hapatectomy 48h ...

- Schug J; McKenna LB; Walton G; Hand N; et al., 2013, BMC genomics.

Article - Schug J; McKenna LB; Walton G; Hand N; et al.
- BMC genomics, 2013
BACKGROUND: Validation of physiologic miRNA targets has been met with significant challenges. We employed HITS-CLIP to identify which miRNAs participate in liver regeneration, and to identify their target mRNAs. RESULTS: miRNA recruitment to the RISC is highly dynamic, changing more than five-fold for several miRNAs. miRNA recruitment to the RISC did not correlate with changes in overall miRNA expression for these dynamically recruited miRNAs, emphasizing the necessity to determine miRNA recruitment to the RISC in order to fully assess the impact of miRNA regulation. We incorporated RNA-seq quantification of total mRNA to identify expression-weighted Ago footprints, and developed a microRNA regulatory element (MRE) prediction algorithm that represents a greater than 20-fold refinement over computational methods alone. These high confidence MREs were used to generate candidate 'competing endogenous RNA' (ceRNA) networks. CONCLUSION: HITS-CLIP analysis provide novel insights into global miRNA:mRNA relationships in the regenerating liver.
LinkOut: [PMID: 23597149]
46 mmu-miR-186-5p Target Genes:
Functional analysis:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT577608 Stxbp4 syntaxin binding protein 4 1 1
MIRT577884 Qpct glutaminyl-peptide cyclotransferase (glutaminyl cyclase) 1 1
MIRT578137 Noc3l NOC3 like DNA replication regulator 1 1
MIRT578249 Mnat1 menage a trois 1 1 1
MIRT579147 Ces2g carboxylesterase 2G 1 1
MIRT579219 Ccdc138 coiled-coil domain containing 138 1 1
MIRT579578 4933427D06Rik RIKEN cDNA 4933427D06 gene 1 1
MIRT580348 Tmem33 transmembrane protein 33 1 1
MIRT580592 Tbl1xr1 transducin (beta)-like 1X-linked receptor 1 1 1
MIRT580668 Stk32a serine/threonine kinase 32A 1 1
MIRT580744 Srek1 splicing regulatory glutamine/lysine-rich protein 1 1 1
MIRT580779 Sp6 trans-acting transcription factor 6 1 1
MIRT580847 Sltm SAFB-like, transcription modulator 1 1
MIRT580944 Slc26a5 solute carrier family 26, member 5 1 1
MIRT581214 Samd4 sterile alpha motif domain containing 4 1 1
MIRT581276 Rprd2 regulation of nuclear pre-mRNA domain containing 2 1 1
MIRT581520 Ptprb protein tyrosine phosphatase, receptor type, B 1 1
MIRT582203 Nfia nuclear factor I/A 1 1
MIRT582893 Ildr2 immunoglobulin-like domain containing receptor 2 1 1
MIRT582996 Id4 inhibitor of DNA binding 4 1 1
MIRT583079 Hnrnpa3 heterogeneous nuclear ribonucleoprotein A3 1 1
MIRT583125 Heca hdc homolog, cell cycle regulator 1 1
MIRT583739 Epm2aip1 EPM2A (laforin) interacting protein 1 1 1
MIRT584127 Crispld2 cysteine-rich secretory protein LCCL domain containing 2 1 1
MIRT584166 Cpox coproporphyrinogen oxidase 1 1
MIRT584531 C230081A13Rik pseudopodium-enriched atypical kinase 1 1 1
MIRT584646 Bach2 BTB and CNC homology, basic leucine zipper transcription factor 2 1 1
MIRT587978 Armc1 armadillo repeat containing 1 1 1
MIRT588832 Sp1 trans-acting transcription factor 1 1 2
MIRT590758 Acbd5 acyl-Coenzyme A binding domain containing 5 1 1
MIRT593146 Mmp12 matrix metallopeptidase 12 1 4
MIRT593495 Gjc3 gap junction protein, gamma 3 1 1
MIRT594880 Lrig2 leucine-rich repeats and immunoglobulin-like domains 2 1 1
MIRT594898 Ifi204 interferon activated gene 204 1 1
MIRT594932 Gdi2 guanosine diphosphate (GDP) dissociation inhibitor 2 1 1
MIRT594945 Fmnl2 formin-like 2 1 1
MIRT595197 Emc3 ER membrane protein complex subunit 3 1 1
MIRT595343 Frmd4a FERM domain containing 4A 1 1
MIRT595402 Arsk arylsulfatase K 1 1
MIRT595430 A630033H20Rik RIKEN cDNA A630033H20 gene 1 1
MIRT595947 Nelfa negative elongation factor complex member A, Whsc2 1 1
MIRT596153 Opn5 opsin 5 1 1
MIRT601390 Utp23 UTP23 small subunit processome component 1 1
MIRT602153 Intu inturned planar cell polarity protein 1 1
MIRT602577 Colec12 collectin sub-family member 12 1 1
MIRT604817 Nr5a2 nuclear receptor subfamily 5, group A, member 2 1 1
miRNA-Drug Associations
miRNA Small Melocule FDA CID Detection Method Condition PMID Year Expression Pattern of miRNA
miR-186 Gemcitabine approved 60750 Northern blot Mz-ChA-1 human cholangiocarcinoma cell lines 16762633 2006 down-regulated
miR-186 Formaldehyde NULL 712 Microarray Human lung epithelial cells (A549) 21147603 2011 down-regulated
miR-186 1,2,6-Tri-O-galloyl-beta-D-glucopyranose NULL NULL Microarray HepG2 hepatocarcinoma cells. 22506400 2011 down-regulated
miR-186 Ginsenoside Rh2 NULL 119307 Microarray NSCLC cell line A549 23152132 2013 up-regulated
miR-186 Nicotine approved 89594 Microarray Rat adrenal pheochromocytoma PC12 cell 18845019 2009 down-regulated

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