pre-miRNA Information
pre-miRNA mmu-mir-181b-1   
Genomic Coordinates chr1: 137966639 - 137966718
Description Mus musculus miR-181b-1 stem-loop
Comment Mouse miR-181b was predicted by computational methods using conservation with human and Fugu rubripes sequences .
RNA Secondary Structure
pre-miRNA mmu-mir-181b-2   
Genomic Coordinates chr2: 38853830 - 38853918
Synonyms Mirn181b-2, mir-181b-2, Mir181b-2
Description Mus musculus miR-181b-2 stem-loop
Comment Mouse miR-181b was predicted by computational methods using conservation with human and Fugu rubripes sequences .
RNA Secondary Structure

Mature miRNA Information
Mature miRNA mmu-miR-181b-5p
Sequence 12| AACAUUCAUUGCUGUCGGUGGGU |34
Evidence Experimental
Experiments Cloned
Putative Targets

Biomarker Information
Biomarker ID Name Type Discovered From Mode Level Source Testing Methods
BK9AD8 miR-181b-5p Monitoring Biomarker (MOI) Clinical/Experimental Data Expression Decrease Peripheral blood Quantitative reverse transcription PCR
Gene Information
Gene Symbol Arhgef15   
Synonyms D130071N09, D530030K12Rik, E5
Description Rho guanine nucleotide exchange factor (GEF) 15
Transcript NM_177566   
Expression
Putative miRNA Targets on Arhgef15
3'UTR of Arhgef15
(miRNA target sites are highlighted)
>Arhgef15|NM_177566|3'UTR
   1 GGCAGGCTAGGGAGGAGCACAGATTGGGATACTGGCAGCAGCATGGGGAAGAAAAAGTCTATCCATCCATCTGTCCAACC
  81 GTCCAACCGTCCATCCATCCATCCATCCATCTACTTGCTGTCAGTGGAAACACTACCTCTAGAGGCAACCAATAGGGATA
 161 GAGCAGCTAATGAAACAAGACCATCTGAGCCCACGACAAGGAAGAATGGGGATGGCTCGAATGTGTTGCCAATGGAGACA
 241 GGGGATGAGTACAGAGTGGCCAAGGCTGAGGCCACGGCCAGAGGGTATCAAAGTATGTCCACAACCAAGGAAGATTAAGC
 321 AGGGGCATTGCATTGAGAAATGACGTCATTGAAGTAGTCCTGTAGACAACAGGGATGGGATGGGACCTATCCAGCCAGAG
 401 AAGACGGTGATTTGGGCTCAAGAGAGCAGTAGTCACCCTTGTTGGTTTTACAGAAGCCACTGGTCCTGCTTTTTGAGTAT
 481 AGGAAGTATTAAATTAATCTAATACTTCTGTTTGAGGGCTACTTTCTTTGCCCATTTTAAACCACTTCCTTTCTTCTAGA
 561 AGAATCCAGAGTGCATCTCAGAGAATATGAGTGCATGTGTGTTCATGTATATATGTATCTAGGAAGGCAACTGTGCTGAA
 641 TGTGGTGTGTGTGTGTGTGTGTGTGTGTGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAACGCACCTCTCCCCTC
 721 TCCTGTTGGTGACTGAATACTTCCTTTCCTCTATCATCTCACATTTATCCTCTTATTTTCTCCAAAAAAAGCCATATGCC
 801 CTGAGATCTAAAAAAAGAGTACTGAGCATAGCTTGCCCAAGGACTGGGACCGTGAATGCAAGCCATGGATTCAGGGTCTC
 881 CCGGGTGTCTCTGGGTTCTATGACAGTTGAAAGCTGGTATTATGAAGCAGCTGGTGGCCCGCAAGGAAGGCACTGAGGAC
 961 TAAGCCACTGGGATTTGAGATCCTCAGCAGTCTGTGGACCTCTTCCTGTCCCAGGCATTGACCTCTGTGATCCATGTCTG
1041 CTCTGTGTCATCTCCCGACTTGAATTGTCATCATGATGTCAGCCAGCCTCGGGCTGCAGAACAAGTTGGGTCCTGGGTCA
1121 GCTGGCAACCATCCTGATCTTCTTCTATCCTGATCCTCTCAGAAGCAGAAGGCTGAACCCAGGAGGGAGTAGAGAGCTGA
1201 TGGTGTTACTCAGACTCAACCACGGTTTCTGCTAGAGAACCTGCCCTGTGTGATGCTGGAGCGGTGAAGGCAAAGGCAGT
1281 AGAATAGACAATTGCTGGGCTTGGGGCCCAGACCTGGGCAAAGGCTTTCTAAATCTTCAGGACTGTGCAATACTGTTCCT
1361 TCATGTATGACAACCTGCCCAGATGGAGACTGCTTAGGTGACTATGGGAGGGGTAATGAGTCTGGGGACTTGAAGGCAAT
1441 AGGGCACTTTGTGTGTCCACAGCTTTCATCCAGCAAAGTGCCAGCCACATGGGAAACCCTCAATAAATGTTGCTGGAAAG
1521 AGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
1601 A
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' ugggugGCUGUCGUUACUUACAa 5'
                | || |:: ||||||| 
Target 5' ggaaggCAACTGTGCTGAATGTg 3'
622 - 644 153.00 -9.20
2
miRNA  3' ugGGUGGCUGUC---GUUACUUACaa 5'
            |||  ||| |   | :||||||  
Target 5' gcCCAAGGACTGGGACCGTGAATGca 3'
835 - 860 137.00 -16.10
3
miRNA  3' ugGGUG---GCU---GUCGUUACUUACAa 5'
            ||||    ||   |  |||| ||||| 
Target 5' agCCACATGGGAAACCCTCAATAAATGTt 3'
1483 - 1511 125.00 -13.90
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_BrainB_130_50. RNA binding protein: AGO. Condition:Brain B 2A8 P13 130 KD HITS-CLIP data was present in Chi_BrainC_130_50. RNA binding protein: AGO. Condition:Brain C 2A8 P13 130 KD ...

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

miRNA-target interactions (Provided by authors)
ID Duplex structure Position
1
miRNA  3' uggguggcuguCGUUACUUACAa 5'
                     |:::|| :||| 
Target 5' ---------auGUGGUGUGUGUg 3'
1 - 14
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 ...

- 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 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 ERR266281. RNA binding protein: AGO2. Condition:A_Liver partial hapatectomy 48h HITS-CLIP data was present in ERR266286. RNA binding protein: AGO2. Condition:A_Liver partial hapatectomy 1h 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 HITS-CLIP data was present in ERR266295. RNA binding protein: AGO2. Condition:B_Liver partial hapatectomy 1h HITS-CLIP data was present in ERR266298. RNA binding protein: AGO2. Condition:A_Untreated HITS-CLIP data was present in ERR266300. RNA binding protein: AGO2. Condition:B_Untreated ...

- 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]
Experimental Support 4 for Functional miRNA-Target Interaction
miRNA:Target ----
Validation Method
     
Conditions C2C12
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 GSM1385342. RNA binding protein: 聽AGO2. Condition:C2C12_GM_Ago2_CLIP-Seq_myoblast HITS-CLIP data was present in GSM1385343. RNA binding protein: 聽AGO2. Condition:C2C12_DM_Ago2_CLIP-Seq_myotubes ...

- Zhang X; Zuo X; Yang B; Li Z; Xue Y; Zhou et al., 2014, Cell.

Article - Zhang X; Zuo X; Yang B; Li Z; Xue Y; Zhou et al.
- Cell, 2014
MicroRNAs are well known to mediate translational repression and mRNA degradation in the cytoplasm. Various microRNAs have also been detected in membrane-compartmentalized organelles, but the functional significance has remained elusive. Here, we report that miR-1, a microRNA specifically induced during myogenesis, efficiently enters the mitochondria where it unexpectedly stimulates, rather than represses, the translation of specific mitochondrial genome-encoded transcripts. We show that this positive effect requires specific miR:mRNA base-pairing and Ago2, but not its functional partner GW182, which is excluded from the mitochondria. We provide evidence for the direct action of Ago2 in mitochondrial translation by crosslinking immunoprecipitation coupled with deep sequencing (CLIP-seq), functional rescue with mitochondria-targeted Ago2, and selective inhibition of the microRNA machinery in the cytoplasm. These findings unveil a positive function of microRNA in mitochondrial translation and suggest a highly coordinated myogenic program via miR-1-mediated translational stimulation in the mitochondria and repression in the cytoplasm.
LinkOut: [PMID: 25083871]
56 mmu-miR-181b-5p Target Genes:
Functional analysis:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT004755 Timp3 tissue inhibitor of metalloproteinase 3 4 1
MIRT005296 Aicda activation-induced cytidine deaminase 5 1
MIRT005300 Slc35d3 solute carrier family 35, member D3 2 1
MIRT005301 Ak4 adenylate kinase 4 2 1
MIRT005302 Ndrg1 N-myc downstream regulated gene 1 2 1
MIRT005303 Pitpnc1 phosphatidylinositol transfer protein, cytoplasmic 1 2 1
MIRT005304 Tmem14a transmembrane protein 14A 2 1
MIRT005305 Cd244 CD244 natural killer cell receptor 2B4 2 1
MIRT005306 Gch1 GTP cyclohydrolase 1 2 1
MIRT005307 Errfi1 ERBB receptor feedback inhibitor 1 2 1
MIRT005308 Hk2 hexokinase 2 2 1
MIRT005309 Mxi1 MAX interactor 1, dimerization protein 2 1
MIRT005310 Ccdc58 coiled-coil domain containing 58 2 1
MIRT005311 Sc4mol methylsterol monoxygenase 1 2 1
MIRT005312 Pfkfb3 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 2 1
MIRT005313 Pdxp pyridoxal (pyridoxine, vitamin B6) phosphatase 2 1
MIRT005314 Atp5g1 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C1 (subunit 9) 2 1
MIRT005315 Casp3 caspase 3 2 1
MIRT005316 Ulk3 unc-51-like kinase 3 2 1
MIRT005317 Snx25 sorting nexin 25 2 1
MIRT005318 Higd1a HIG1 domain family, member 1A 2 1
MIRT006312 Cbx7 chromobox 7 2 1
MIRT438370 SIX2 SIX homeobox 2 3 1
MIRT438687 Hspa5 heat shock protein 5 3 1
MIRT438688 Uchl1 ubiquitin carboxy-terminal hydrolase L1 3 1
MIRT577184 Smarca4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 1 5
MIRT577425 Tulp3 tubby-like protein 3 1 1
MIRT578325 Magea5 melanoma antigen, family A, 5 1 1
MIRT579346 Arhgef15 Rho guanine nucleotide exchange factor (GEF) 15 1 4
MIRT580671 Stk32a serine/threonine kinase 32A 1 1
MIRT580762 Spp1 secreted phosphoprotein 1 1 1
MIRT581071 Sgpp1 sphingosine-1-phosphate phosphatase 1 1 1
MIRT582047 Osbpl3 oxysterol binding protein-like 3 1 1
MIRT582656 Lnp lunapark, ER junction formation factor 1 2
MIRT583661 Fam160b2 family with sequence similarity 160, member B2 1 5
MIRT583691 Fam122b family with sequence similarity 122, member B 1 1
MIRT584580 Bnc2 basonuclin 2 1 1
MIRT584878 Ap1g1 adaptor protein complex AP-1, gamma 1 subunit 1 1
MIRT586224 Ptchd2 dispatched RND transporter family member 3 1 2
MIRT587223 Fam69c family with sequence similarity 69, member C 1 1
MIRT588616 Trim2 tripartite motif-containing 2 1 1
MIRT589131 Rad51d RAD51 paralog D 1 1
MIRT589794 Ikzf2 IKAROS family zinc finger 2 1 2
MIRT590593 Atp2a2 ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 1 1
MIRT591186 Ms4a4c membrane-spanning 4-domains, subfamily A, member 4C 1 3
MIRT591489 Aqp3 aquaporin 3 1 2
MIRT592858 Adamts9 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 9 1 2
MIRT594856 Nacc1 nucleus accumbens associated 1, BEN and BTB (POZ) domain containing 1 1
MIRT594983 Ebf3 early B cell factor 3 1 1
MIRT596592 Zfp689 zinc finger protein 689 1 1
MIRT598537 Itpk1 inositol 1,3,4-triphosphate 5/6 kinase 1 1
MIRT598728 H2-D1 histocompatibility 2, D region locus 1 1 1
MIRT600002 4930563E22Rik RIKEN cDNA 4930563E22 gene 1 1
MIRT603966 Gpd1l glycerol-3-phosphate dehydrogenase 1-like 1 1
MIRT605134 Clmn calmin 1 1
MIRT606009 Dagla diacylglycerol lipase, alpha 1 1
miRNA-Drug Associations
miRNA Small Melocule FDA CID Detection Method Condition PMID Year Expression Pattern of miRNA
miR-181b Teniposide approved 452548 Quantitative real-time PCR glioma cells 25151861 2014 up-regualted
miR-181b All-trans-retinoic acid (ATRA) approved 444795 Microarray acute promyelocytic leukemia 17260024 2008 down-regulated
miR-181b Curcumin NULL 969516 Microarray BxPC-3 human pancreatic carcinoma cell line 18347134 2008 up-regulated
miR-181b Trichostatin A (TSA) NULL 444732 Microarray human pancreatic cancer cell line BxPC-3 19112422 2009 down-regulated
miR-181b Doxorubicin approved 31703 Microarray ovarian cancer 19237188 2009 up-regulated
miR-181b Gemcitabine approved 60750 Microarray ovarian cancer 19237188 2009 up-regulated
miR-181b All-trans-retinoic acid (ATRA) approved 444795 Quantitative real-time PCR acute promyelocytic leukemia (APL) 19749800 2009 down-regulated
miR-181b Morphine approved 5288826 Microarray human monocyte-derived macrophages (h-mdms) infection with HIV-1 20564181 2010 down-regulated
miR-181b Formaldehyde NULL 712 Microarray Human lung epithelial cells (A549) 21147603 2011 down-regulated
miR-181b Enoxacin approved 3229 Quantitative real-time PCR HCT-116 and RKO colon cancer cell lines 21368194 2011 up-regulated
miR-181b Ginsenoside Rh2 NULL 119307 Microarray human glioma cells U251 21372826 2011 up-regulated
miR-181b Aidi injection NULL NULL Microarray human breast cancer cells 21563499 2011 down-regulated
miR-181b Arsenic trioxide approved 14888 Quantitative real-time PCR acute promyelocytic leukemia 22072212 2012 up-regulated
miR-181b Olea europaea leaf extract NULL NULL Quantitative real-time PCR glioblastoma cells. 22722712 2012 up-regulated
miR-181b Temozolomide approved 5394 Quantitative real-time PCR glioblastoma cells. 22722712 2012 up-regulated
miR-181b Celecoxib approved 2662 Microarray gastric cancer cells. 23001726 2013 up-regulated
miR-181b 17beta-estradiol (E2) approved 5757 Microarray rat breast 17700064 2007 up-regulated
miR-181b Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) NULL 8490 Microarray mouse brain 19270793 2009 down-regulated
miR-181b Estrogen NULL NULL Microarray mouse uterus 20720260 2010 down-regulated
miR-181b Estrogen NULL NULL Quantitative real-time PCR mouse uterus 20720260 2010 down-regulated
miR-181b Reversine NULL 210332 Microarray C2C12 myoblast cells 24513286 2014 down-regulated
miR-181b Nicotine approved 89594 Microarray Rat adrenal pheochromocytoma PC12 cell 18845019 2009 up-regulated
miR-181b Perfluorooctane sulfonate NULL 74483 Microarray zebrafish embryos 20878907 2011 down-regulated
miR-181b Perfluorooctane sulfonate NULL 74483 Quantitative real-time PCR zebrafish embryos 20878907 2011 down-regulated
miR-181b Marine fungal metabolite 1386A NULL NULL Microarray MCF-7 breast cancer cells. 22159329 2012 up-regulated
miRNA-Drug Resistance Associations
miRNA Drug Name CID NSC FDA Effect/Pattern Detection Method Level Phenotype Condition
mmu-miR-181b-5p Gemcitabine 60750 NSC613327 approved sensitive Low Pancreatic Ductal Adenocarcinoma tissue and cell line (SW1990, CFPAC-1)

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