pre-miRNA Information
pre-miRNA mmu-mir-874   
Genomic Coordinates chr13: 58023125 - 58023200
Synonyms Mirn874, mmu-mir-874, Mir874
Description Mus musculus miR-874 stem-loop
Comment None
RNA Secondary Structure

Mature miRNA Information
Mature miRNA mmu-miR-874-3p
Sequence 45| CUGCCCUGGCCCGAGGGACCGA |66
Evidence Experimental
Experiments Cloned
Putative Targets

Gene Information
Gene Symbol Pdk1   
Synonyms B830012B01, D530020C15Rik
Description pyruvate dehydrogenase kinase, isoenzyme 1
Transcript NM_172665   
Expression
Putative miRNA Targets on Pdk1
3'UTR of Pdk1
(miRNA target sites are highlighted)
>Pdk1|NM_172665|3'UTR
   1 ACGCACATGGGACGCCTGGCACATCCACATGTGGTTTCTGCTAAATTTGGAAGACATGTATTTGGAACCACACTGTTCCA
  81 AATATTTCACGTGTGATCTTCACAATTAGTGTTTGCTGAAGCTCCTAAAGGATCGGTTATGCCAACTGTATTCTGATGTG
 161 TTGGGTTAATTGGGCGTGGTTTTGAACACACATAATTTTGGTCAACTACCCTTGGTATGGTATGGGGTGTGAAGTTCCTG
 241 GTTTCTGTAGGAAGCTGAGTATTTCTTTCAAGTTTTCACTTACTTCTGCTAGAAGCATCTGAAGAACGTGGAGTAGCTGG
 321 CTAGCGGCCTCTCTGCTTTTGGAGTTCTATCATCTGTGAGTGGTGACACCTAGTCAGATGGTCTTCTTATCTCCCACGAA
 401 GAACAACACAGTGATCCGTTAGAACCCACACAGGTTGTCAGAGTGCTGAAATGAATTGATCATGGCATCATTTTTTTGCA
 481 GTGGATTGTAATGACTGGTTCCCCATGGAGCTAAGTCCAGAGCGTGGTTATCGAGTTTACTGTCAGCACAAGGGATTTTC
 561 TTTAAAAACAAAGTCTCACTGTGTAGCCCCAGCTGGCCTTGAGCTTACAAAGCCCTCGGTGTCCTGAGCGCTGGAATGAG
 641 AAGGGTGTGCCACCACATCTGGCTTACAAGAGAAACGTTAGTCCCAAAACAAGCCAAATGGCAGCAGAGAGTAAACTGTT
 721 TGGGAAGCACCAAGTGGCCCAGGCCGAGCTGACCGACTGCTGAGGTGATCTGAGGATGAGCGTGAGATTCTCTGGGTCCC
 801 ACCCAGGGATCCAGAGGCTGAAGGCCAGGGACCAGGTGAGGCTCATGGCTGGCCTGGCTGGAACTATATTTGGGAGTGAA
 881 TCGTGACTACTGCTGTTGTCAGAGTGACAGACTAGATTGGGAAGCTTGTCGGGTTGCTACACATTAGGGGACATAATCTG
 961 AATCTCAAGCCTGGTGCAAGCTAAAGCATTAGCGGGAAGACCAGGGTGACAGCGAGAGGTCAGGTGACCAAAGGCTCAGC
1041 CACCTTGGTTTCCAGTGGTGACTAAGAACATGTATTTTTCTAAAATATCCAGATTTTTTTTTTAAATCAAAGAAAAGTCA
1121 GCTTATATTAACTACAGAATTCATTTGCAGCTATGTGTTGATTTAAAGTCTGCAACAAACGCTTTGAAGTATTGATGTTA
1201 TTTGTGTTAGAATACAAACCTATGGAGCAGGTAATGACACCTGGGTTCTCTCTCAGTGACCCAGAGTCACACAGAATTGG
1281 TGCCCCAGCCTGAGCTGTCTCTGCTGATCACTGTCCACTGTCTGGGATATTTATAACCTCCTCTGTTAGGTGATGGGGAA
1361 GTACTTGGAAAACATGCTTTGCCACTTGCCTAGAGGGATTTGGGGGTTTGGTTTGGAAAATGTAGTGAGTTAAAACATGT
1441 CACTCTTGACATGTTTTATCCAGTCTTCACTCTGTGTCCTACACATACATACATCTGTAATACAAAAGCCAAATCATGTG
1521 ACATGGCACAAAATAGAACTTTGGTGCCAGTGATAGGAACATGCAGCCTGAGCATGCGCCAGGGTGGTCAGCCCAGATCC
1601 TTAGCTGAGAGGTGAGGGGCCTGAAACTCAGGTCCTATTGGCCCAGGGTTTTTAGCTAATACTACCAAATGTTGGAAAAT
1681 ATACACCGTATACCTGCTGTTTCTAATTGAGGACTTTGTAAGAAATAATAGATCATGCTCCTGAGTGGCATTTATTCAGT
1761 GTATTGCACTTACTAGCTTTCAATTACACTTTACTGCAATGATGAAATATTTTGGAATCTTTTGTACAACTGTCAATAAA
1841 CGTACTATTTTTACTTGTGAAATACTTTGCCCTCTCCAAGGAATTAAAAAAAATTATCCCCCTCTCTGCTTAAGAGCTAA
1921 GAAATGTTTTCAGACAAGAAGAATTTAAAATTAGTTTACTTTAGATTCTTTTTAAGGTGTAGCACCTTTTTGCTCTGTTG
2001 TAATGGTAATGGATGGAGACAATGTGACAAAGCTCTAGGGGACGCTTTCCAGAGTTACTTTTAAAGACACCTGGAAGGTT
2081 TTTAGATTCTTAAGGTGAGCCATTTTGTCTGCCAGCGATAGTTTTATGTGGTTTAGGTATGAAAATAGAGTTGATGGTTG
2161 GGGAATGGACAGCAAGTGATTTTTATAACCTGGGCAGTTAGTGAGTGTGCCAGTGTAGTGTAGGAAAGGATTGTAAGAAT
2241 ATTTCACCAGGCAGTGGTGGCGCACGCCTTTAATCCCAACACATGGGAGGCAGAGGCAGGCGGATTTCTGAGGCTAGCCT
2321 GGTCTACAGAATGAGTTCCAGGGCAGCCAGGGCTATACAGAGAAACCCTGTCTCGAAAAATAAAAGACTATTCCACACTG
2401 TAATTCCAAATGCTGGCTGGTTTTGATGCCTTTACATTTAATAATGGTCAGTGTCTTACACTGAGATTTCTACATGAAGA
2481 CATAGAAGCAGAATTCTACCGCAGCGTGGTGCATTTTCGGGGTGACTGAAAACTGAAAAGATGGATCAGCTTTAAAAAAA
2561 AATTTGAGCCACTTAAGGATCTTAGAAATATACTCGTGTCCTTTAGACAGCAGTCTGTTTCATCATCAAGACTCAATATC
2641 TGTACAGGTTCAACGAATTGTAACTAGTTGCCAGCACTGGCTCAGTGGGTAAAAGCATGGCCATCAAGCCTGGGTTAGGG
2721 ATAGGGTTGGAGATCTTTCCTCAGCACGAATGGTGGAATTAGAGAAAGAACCAACCATCCTGTGAGTTATCTGTGGTTCT
2801 CCACACGTGCACTGTGCACATGCGCATCCCCTACATACACCACACTAATAACTGTAGCCAGGTGTCTTGCACTCTCAACC
2881 ATCTCCTAGCAGTGCTTGAGGCAGGCTTGCACTGTAGATAGCCTAGTGGGCAAAGCAGGTAGAGTTCGTGTGCTTAGAGT
2961 TATCCTAGATTTCCCTTTTCTAATACACTGCCAATGATTGACATGTGCTGGAGAACTGGTGGATAATTTTGAAGAGCTGT
3041 ATAAGTAAGTCATTTTCCACAGTAGAAATAACAGTAGGGAAAGGCTTAGTGTAACTGGCACTGCCTTCTACTCAACACTG
3121 GTGGAATCTCCTTTAGTCAAGACAGAGTATGTCCTATTGCTCGTTGATAGCGTGGGTCCACCACGCCTGCCTTTCACCGT
3201 TACAGCGGCATGGCGGCACACACCTGTAAGTAGATCTCTGAGCTTGAGCCAGCCTGGTCAACATAGGGAGTTTCAGGTTA
3281 GCCAAGGCTACATGTACGGACCCTGTGTGCTGTATTTTTTTTTTTTTTAAATCAATGAGGTCTAAAACAACTACAGAGGA
3361 GGAAAGAGTTGTGTGGTTCTATGAAACTCAGTGAGTGGCTAATTAGAGAGGGACCCCAGCCAGCAACCTTCTCTTATGTC
3441 ATCAGGTTTACAAGGAAGTACAAAGCTTGAAAGGAGAGGTGGCCAGGGTTAGGTTTGGTTGTTTTAACTGAAGGAACTTC
3521 TCATATCCGATTAACTTGTGTTCTCAATACTATTAATTCTTCTCTCAGTCAAACCCAAGACACTATAAAAAAAATAGAAT
3601 TAATGCTTTGTGAAGGAAAACAACGCATTGCTATTTTACACAATCCTGGCATTCTTAAATGACTGTATCACTTGTTCTAC
3681 CTTTTGTGTTTGCAAAGAATTAAACAGTGTGCTGTCCACTTTTCTTTGCCTGTAAAAAAAAAAAAAAAAAA
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' agCCAGG-G---AGCCC--GGUCCCGUc 5'
            ||||: |    :| |  |||||||| 
Target 5' ctGGTCTACAGAATGAGTTCCAGGGCAg 3'
2319 - 2346 146.00 -24.00
2
miRNA  3' agCCAGGG-AGCCCGGUCCCGuc 5'
            |||||: |:|| ||||||:  
Target 5' caGGTCCTATTGGCCCAGGGTtt 3'
1629 - 1651 140.00 -27.50
3
miRNA  3' agCCAGGGAGCCCGGUCCCguc 5'
            |||||| |   ||||||   
Target 5' tgGGTCCCAC---CCAGGGatc 3'
793 - 811 125.00 -21.92
Experimental Support 1 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 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 2 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 ...

- 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]
11 mmu-miR-874-3p Target Genes:
Functional analysis:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT581679 Ppp1r3d protein phosphatase 1, regulatory subunit 3D 1 1
MIRT586364 Pdk1 pyruvate dehydrogenase kinase, isoenzyme 1 1 2
MIRT588099 Afg3l1 AFG3-like AAA ATPase 1 1 2
MIRT589856 Hexim1 hexamethylene bis-acetamide inducible 1 1 1
MIRT591274 Lars2 leucyl-tRNA synthetase, mitochondrial 1 2
MIRT593523 Cmklr1 chemokine-like receptor 1 1 1
MIRT594608 Pak6 p21 protein (Cdc42/Rac)-activated kinase 6 1 1
MIRT595052 Bace1 beta-site APP cleaving enzyme 1 1 1
MIRT602654 Cass4 Cas scaffolding protein family member 4 1 1
MIRT602897 2610034B18Rik actin-related protein 2/3 complex inhibitor 1 1
MIRT734518 IDO1 indoleamine 2,3-dioxygenase 1 2 0
miRNA-Drug Associations
miRNA Small Melocule FDA CID Detection Method Condition PMID Year Expression Pattern of miRNA
miR-874 Budesonide approved 5281004 Microarray neonatal mice liver 20145010 2010 down-regulated
miR-874 Tert-butyl hydroperoxide (t-BHP) NULL 6410 Microarray mouse auditory cells 20510889 2010 down-regulated
miR-874 Glucose NULL 5793 Quantitative real-time PCR endothelial cells 24394957 2014 down-regulated
miR-874 Lenalidomide approved 216326 Quantitative real-time PCR peripheral blood CD14+ monocytes 25287904 2014 down-regulated
miR-874 Mistletoe lectin-I NULL NULL Microarray colorectal cancer cells CLY cells 20955366 2011 down-regulated
miR-874 FdUMP[10] NULL 25244711 Microarray NCI-60 cell-line 21159603 2011 up-regulated
miR-874 Floxuridine (FdU) approved 5790 Microarray NCI-60 cell-line 21159603 2011 up-regulated
miR-874 Irinotecan approved 60838 Microarray NCI-60 cell-line 21159603 2011 up-regulated
miR-874 Topotecan approved 60700 Microarray NCI-60 cell-line 21159603 2011 up-regulated

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