Accession ID: MIRT000032 [miRNA, hsa-miR-7 :: SNCA, target gene]
|Synonyms||MGC110988, NACP, PARK1, PARK4, PD1|
|Description||synuclein, alpha (non A4 component of amyloid precursor)|
|Other Transcripts||NM_001146054, NM_001146055, NM_007308|
hsa05010 Alzheimer's disease - Homo sapiens (human)
hsa05012 Parkinson's disease - Homo sapiens (human)
|Putative miRNA Targets on SNCA|
|3'UTR of SNCA
(miRNA target sites are highlighted)
>SNCA|NM_000345|3'UTR 1 TAAGAAATATCTTTGCTCCCAGTTTCTTGAGATCTGCTGACAGATGTTCCATCCTGTACAAGTGCTCAGTTCCAATGTGC 81 CCAGTCATGACATTTCTCAAAGTTTTTACAGTGTATCTCGAAGTCTTCCATCAGCAGTGATTGAAGTATCTGTACCTGCC 161 CCCACTCAGCATTTCGGTGCTTCCCTTTCACTGAAGTGAATACATGGTAGCAGGGTCTTTGTGTGCTGTGGATTTTGTGG 241 CTTCAATCTACGATGTTAAAACAAATTAAAAACACCTAAGTGACTACCACTTATTTCTAAATCCTCACTATTTTTTTGTT 321 GCTGTTGTTCAGAAGTTGTTAGTGATTTGCTATCATATATTATAAGATTTTTAGGTGTCTTTTAATGATACTGTCTAAGA 401 ATAATGACGTATTGTGAAATTTGTTAATATATATAATACTTAAAAATATGTGAGCATGAAACTATGCACCTATAAATACT 481 AAATATGAAATTTTACCATTTTGCGATGTGTTTTATTCACTTGTGTTTGTATATAAATGGTGAGAATTAAAATAAAACGT 561 TATCTCATTGCAAAAATATTTTATTTTTATCCCATCTCACTTTAATAATAAAAATCATGCTTATAAGCAACATGAATTAA 641 GAACTGACACAAAGGACAAAAATATAAAGTTATTAATAGCCATTTGAAGAAGGAGGAATTTTAGAAGAGGTAGAGAAAAT 721 GGAACATTAACCCTACACTCGGAATTCCCTGAAGCAACACTGCCAGAAGTGTGTTTTGGTATGCACTGGTTCCTTAAGTG 801 GCTGTGATTAATTATTGAAAGTGGGGTGTTGAAGACCCCAACTACTATTGTAGAGTGGTCTATTTCTCCCTTCAATCCTG 881 TCAATGTTTGCTTTACGTATTTTGGGGAACTGTTGTTTGATGTGTATGTGTTTATAATTGTTATACATTTTTAATTGAGC 961 CTTTTATTAACATATATTGTTATTTTTGTCTCGAAATAATTTTTTAGTTAAAATCTATTTTGTCTGATATTGGTGTGAAT 1041 GCTGTACCTTTCTGACAATAAATAATATTCGACCATGAATAAAAAAAAAAAAAAAGTGGGTTCCCGGGAACTAAGCAGTG 1121 TAGAAGATGATTTTGACTACACCCTCCTTAGAGAGCCATAAGACACATTAGCACATATTAGCACATTCAAGGCTCTGAGA 1201 GAATGTGGTTAACTTTGTTTAACTCAGCATTCCTCACTTTTTTTTTTTAATCATCAGAAATTCTCTCTCTCTCTCTCTCT 1281 TTTTCTCTCGCTCTCTTTTTTTTTTTTTTTTTACAGGAAATGCCTTTAAACATCGTTGGAACTACCAGAGTCACCTTAAA 1361 GGAGATCAATTCTCTAGACTGATAAAAATTTCATGGCCTCCTTTAAATGTTGCCAAATATATGAATTCTAGGATTTTTCC 1441 TTAGGAAAGGTTTTTCTCTTTCAGGGAAGATCTATTAACTCCCCATGGGTGCTGAAAATAAACTTGATGGTGAAAAACTC 1521 TGTATAAATTAATTTAAAAATTATTTGGTTTCTCTTTTTAATTATTCTGGGGCATAGTCATTTCTAAAAGTCACTAGTAG 1601 AAAGTATAATTTCAAGACAGAATATTCTAGACATGCTAGCAGTTTATATGTATTCATGAGTAATGTGATATATATTGGGC 1681 GCTGGTGAGGAAGGAAGGAGGAATGAGTGACTATAAGGATGGTTACCATAGAAACTTCCTTTTTTACCTAATTGAAGAGA 1761 GACTACTACAGAGTGCTAAGCTGCATGTGTCATCTTACACTAGAGAGAAATGGTAAGTTTCTTGTTTTATTTAAGTTATG 1841 TTTAAGCAAGGAAAGGATTTGTTATTGAACAGTATATTTCAGGAAGGTTAGAAAGTGGCGGTTAGGATATATTTTAAATC 1921 TACCTAAAGCAGCATATTTTAAAAATTTAAAAGTATTGGTATTAAATTAAGAAATAGAGGACAGAACTAGACTGATAGCA 2001 GTGACCTAGAACAATTTGAGATTAGGAAAGTTGTGACCATGAATTTAAGGATTTATGTGGATACAAATTCTCCTTTAAAG 2081 TGTTTCTTCCCTTAATATTTATCTGACGGTAATTTTTGAGCAGTGAATTACTTTATATATCTTAATAGTTTATTTGGGAC 2161 CAAACACTTAAACAAAAAGTTCTTTAAGTCATATAAGCCTTTTCAGGAAGCTTGTCTCATATTCACTCCCGAGACATTCA 2241 CCTGCCAAGTGGCCTGAGGATCAATCCAGTCCTAGGTTTATTTTGCAGACTTACATTCTCCCAAGTTATTCAGCCTCATA 2321 TGACTCCACGGTCGGCTTTACCAAAACAGTTCAGAGTGCACTTTGGCACACAATTGGGAACAGAACAATCTAATGTGTGG 2401 TTTGGTATTCCAAGTGGGGTCTTTTTCAGAATCTCTGCACTAGTGTGAGATGCAAACATGTTTCCTCATCTTTCTGGCTT 2481 ATCCAGTATGTAGCTATTTGTGACATAATAAATATATACATATATGAAAATA
|miRNA:Target||hsa-miR-7 :: SNCA [ Functional MTI ]|
|Validation Method||qRT-PCR , Luciferase reporter assay , Western blot|
|Location of target site||3'UTR, unknown|
|Tools used in this research||miRanda, TargetScan, PicTar, miRBase Target Database,|
|Original Description (Extracted from the article)||... Here, we show that microRNA-7 (miR-7),which is expressed mainly in neurons, represses -synuclein protein levels through the 3-untranslated region (UTR) of -synuclein mRNA. ...
- Junn, E. Lee, K. W. Jeong, B. S. Chan, T. et al., 2009, Proc Natl Acad Sci U S A.
- Proc Natl Acad Sci U S A, 2009
alpha-Synuclein is a key protein in Parkinson's disease (PD) because it accumulates as fibrillar aggregates in pathologic hallmark features in affected brain regions, most notably in nigral dopaminergic neurons. Intraneuronal levels of this protein appear critical in mediating its toxicity, because multiplication of its gene locus leads to autosomal dominant PD, and transgenic animal models overexpressing human alpha-synuclein manifest impaired function or decreased survival of dopaminergic neurons. Here, we show that microRNA-7 (miR-7), which is expressed mainly in neurons, represses alpha-synuclein protein levels through the 3'-untranslated region (UTR) of alpha-synuclein mRNA. Importantly, miR-7-induced down-regulation of alpha-synuclein protects cells against oxidative stress. Further, in the MPTP-induced neurotoxin model of PD in cultured cells and in mice, miR-7 expression decreases, possibly contributing to increased alpha-synuclein expression. These findings provide a mechanism by which alpha-synuclein levels are regulated in neurons, have implications for the pathogenesis of PD, and suggest miR-7 as a therapeutic target for PD and other alpha-synucleinopathies.LinkOut: [PMID: 19628698]
|miRNA:Target||hsa-miR-7 :: SNCA [ Functional MTI ]|
|Validation Method||Immunocytochemistry , Luciferase reporter assay , qRT-PCR , Western blot|
|Location of target site||3'UTR|
|Tools used in this research||miRanda, PicTar, TargetScan|
|Original Description (Extracted from the article)||... Mir-7 and Mir-153 Post-transcriptionally Control SNCA Expression via Its 3'-UTR// Mir-7 and Mir-153 Regulate Endogenous SNCA Protein Levels in Neurons// This study has revealed a previously unknown mechanism by which SNCA levels are regulated in the nervous system. Specifically, two brain-enriched miRNAs, mir-7 and mir-153, have been shown to bind directly to the 3'-UTR of SNCA mRNA and significantly reduce its levels// ...
- Doxakis, E., 2010, J Biol Chem.
|miRNA-target interactions (Provided by authors)||
- J Biol Chem, 2010
Genetic and biochemical studies have established a central role for alpha-synuclein accumulation in the pathogenesis of Parkinson disease. Here, two microRNAs, namely mir-7 and mir-153, have been identified to regulate alpha-synuclein levels post-transcriptionally. These microRNAs bind specifically to the 3'-untranslated region of alpha-synuclein and down-regulate its mRNA and protein levels, with their effect being additive. They are expressed predominantly in the brain with a pattern that mirrors synuclein expression in different tissues as well as during neuronal development, indicating that they play a tuning role in the amount of alpha-synuclein produced. Overexpression of mir-7 and mir-153 significantly reduces endogenous alpha-synuclein levels, whereas inhibition of mir-7 and mir-153 enhances translation of a luciferase construct bearing the alpha-synuclein 3'-untranslated region in primary neurons. These findings reveal a significant additional mechanism by which alpha-synuclein is regulated and point toward new therapeutic regimes for lowering endogenous alpha-synuclein levels in patients with familial or sporadic Parkinson disease.LinkOut: [PMID: 20106983]