Accession ID: MIRT005527 [miRNA, hsa-miR-29c :: FGA, target gene]
pre-miRNA Information
pre-miRNA ID hsa-mir-29c LinkOut: [miRBase ]
Description Homo sapiens miR-29c stem-loop
Comment The mature sequence shown here represents the most commonly cloned form from large-scale cloning studies .
2nd Structure of pre-miRNA
Mature miRNA Information
Mature miRNA hsa-miR-29c-3p
Mature Sequence 54| UAGCACCAUUUGAAAUCGGUUA |75
Evidence Experimental
Experiments Cloned
Putative hsa-miR-29c-3p Targets LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ]
Mature miRNA hsa-miR-29c-5p
Mature Sequence 16| UGACCGAUUUCUCCUGGUGUUC |37
Evidence Experimental
Experiments Cloned
Putative hsa-miR-29c-5p Targets LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ]
miRNA-target interaction network
Gene Information
Gene Symbol FGA LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ]
Synonyms Fib2, MGC119422, MGC119423, MGC119425
Description fibrinogen alpha chain
Transcript NM_000508   LinkOut: [ RefSeq ]
Other Transcripts NM_021871   
Expression LinkOut: [ BioGPS ]
KEGG Pathway hsa04610    Complement and coagulation cascades - Homo sapiens (human)
Putative miRNA Targets on FGA LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ]
3'UTR of FGA
(miRNA target sites are highlighted)
>FGA|NM_000508|3'UTR
   1 TAGGCTGAAGAAGTGGGAATGGGAGCACTCTGTCTTCTTTGCTAGAGAAGTGGAGAGAAAATACAAAAGGTAAAGCAGTT
  81 GAGATTCTCTACAACCTAAAAAATTCCTAGGTGCTATTTTCTTATCCTTTGTACTGTAGCTAAATGTACCTGAGACATAT
 161 TAGTCTTTGAAAAATAAAGTTATGTAAGGTTTTTTTTATCTTTAAATAGCTCTGTGGGTTTTAACATTTTTATAAAGATA
 241 TACCAAGGGCCATTCAGTACATCAGGAAAGTGGCAGACAGAAGCTTCTCTCTGCAACCTTGAAGACTATTGGTTTGAGAA
 321 CTTCTCTTCCCATACCACCCAAAATCATAATGCCATTGGAAAGCAAAAAGTTGTTTTATCCATTTGATTTGAATTGTTTT
 401 AAGCCAATATTTTAAGGTAAAACTCACTGAATCTAACCATAGCTGACCTTTGTAGTAGAATTTACAACTTATAATTACAA
 481 TGCACAATTTATAATTACAATATGTATTTATGTCTTTTGCTATGGAGCAAATCCAGGAAGGCAAGAGAAACATTCTTTCC
 561 TAAATATAAATGAAAATCTATCCTTTAAACTCTTCCACTAGACGTTGTAATGCACACTTATTTTTTTCCCAAGGAGTAAC
 641 CAATTTCTTTCTAAAACACATTTAAAATTTTAAAACTATTTATGAATATTAAAAAAAGACATAATTCACACATTAATAAA
 721 CAATCTCCCAAGTATTGATTTAACTTCATTTTTCTAATAATCATAAACTATATTCTGTGACATGCTAATTATTATTAAAT
 801 GTAAGTCGTTAGTTCGAAAGCCTCTCACTAAGTATGATCTATGCTATATTCAAAATTCAACCCATTTACTTTGGTCAATA
 881 TTTGATCTAAGTTGCATCTTTAATCCTGGTGGTCTTGCCTTCTGATTTTTAATTTGTATCCTTTTCTATTAAGATATATT
 961 TGTCATTTTCTCTTGAATATGTATTAAAATATCCCAAGC
Target sites Provided by authors  Predicted by miRanda
miRNA-target interactions (Predicted by miRanda)
IDDuplex structurePositionScoreMFE
1
miRNA  3' auuggcUAAAGUUUACCACGAu 5'
                ||| | |  |||||| 
Target 5' taaaaaATTCCTA--GGTGCTa 3'
97 - 116 123.00 -10.60
2
miRNA  3' auuggcUA-AAGUU--UACCACGAu 5'
                || ||:||   ||||| | 
Target 5' agttgcATCTTTAATCCTGGTGGTc 3'
890 - 914 118.00 -7.00
3
miRNA  3' auUGGCUAAAGUUUACCAcgau 5'
            ||| ||||    ||||    
Target 5' caACCCATTTACTTTGGTcaat 3'
858 - 879 100.00 -7.56
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-29c :: FGA    [ Functional MTI ]
Validation Method Luciferase reporter assay
Conditions HuH7, HEK-293T
Location of target site 3'UTR
Tools used in this research TargetScan,
Original Description (Extracted from the article) ... In agreement with the TargetScan prediction, we detected a direct effect of hsa-miR-29c (hsa- miR-29a and hsa-miR-29b were not tested) on luciferase activity from the reporter plasmid carrying the FGA-αE-3'UTR but not for the reporter plasmids carrying the other fibrinogen mRNA 3'UTRs (Figure 3A).//We observed significant 24%, 30% and 30% decreases in fibrinogen production when HuH7 cells were transfected with 30 nM of hsa-miR-29c, hsa-miR-29a and hsa-miR- 29b respectively, compared to cells transfected with a negative control precursor molecule (Figure 2A). A similar effect was also observed at lower concentrations (3.3 nM and 10 nM). These results confirm that transfection of hsa-miR-29 family members can reduce fibrinogen production.//Compared to the control condition transfected with hsa-miR-144, a decrease of all five fibrinogen transcripts was observed when HuH7 cells were transfected with hsa-miR-29a, hsa-miR-29b or hsa-miR-29c (Figure 2B). The FGB mRNA level is on average reduced by 56% compared to the non-transfected control, while FGA and FGG transcript levels show reductions of 51% and 42% respectively. ...

- Fort, A. Borel, C. Migliavacca, E. et al., 2010, Blood.

Article - Fort, A. Borel, C. Migliavacca, E. et al.
- Blood, 2010
Elevated levels of fibrinogen are associated with increased risk of cardiovascular disease, whereas low fibrinogen can lead to a bleeding disorder. We investigated whether microRNAs (miRNAs), known to act as post-transcriptional regulators of gene expression, regulate fibrinogen production. Using transfection of a library of 470 annotated human miRNA precursor molecules in HuH7 hepatoma cells, and quantitative measurements of fibrinogen production, we identified 23 miRNAs with down-regulating (up to 64% decrease) and 4 with up-regulating effects (up to 129% increase) on fibrinogen production. Among the downregulating miRNAs, we investigated the mechanism of action of three hsa-miR-29 family members and hsa-miR-409-3p. Overexpression of hsa-miR-29 members lead to decreased steady-state levels of all fibrinogen gene (FGA, FGB, FGG) transcripts in HuH7 cells. Luciferase reporter gene assays demonstrated that this was independent of miRNA-fibrinogen 3'UTR interactions. In contrast, overexpression of hsa-miR-409-3p specifically lowered fibrinogen Bbeta (FGB) mRNA levels and this effect was dependent on a target site in the FGB mRNA 3'UTR. This study adds to the known mechanisms that control fibrinogen production, points towards a potential cause of variable circulating fibrinogen levels, and demonstrates that a screening approach can identify miRNAs that regulate clinically important proteins.
LinkOut: [PMID: 20570858]