mir-133 microRNA precursor family | |
---|---|
Identifiers | |
Symbol | mir-133 |
Rfam | RF00446 |
miRBase | MI0000450 |
miRBase family | MIPF0000029 |
Other data | |
RNA type | Gene; miRNA |
Domain(s) | Eukaryota |
GO | GO:0035195 GO:0035068 |
SO | SO:0001244 |
PDB structures | PDBe |
mir-133 is a type of non-coding RNA called a microRNA that was first experimentally characterised in mice. [1] Homologues have since been discovered in several other species including invertebrates such as the fruitfly Drosophila melanogaster . Each species often encodes multiple microRNAs with identical or similar mature sequence. For example, in the human genome there are three known miR-133 genes: miR-133a-1, miR-133a-2 and miR-133b found on chromosomes 18, 20 and 6 respectively. The mature sequence is excised from the 3' arm of the hairpin. miR-133 is expressed in muscle tissue and appears to repress the expression of non-muscle genes. [2]
It is proposed that Insulin activates the translocation of SREBP-1c (BHLH) active form from the endoplasmic reticulum (ER) to the nucleus and, concomitantly, induces SREPB-1c expression via PI3K signaling pathway. SREBP-1c mediates MEF2C downregulation through a mechanism that remains to be determined. As a consequence of lower MEF2C binding on their enhancer region, the transcription of miR-1 and miR-133a is reduced, leading to decreased levels of their mature forms in muscle, after insulin treatment. Altered activation of PI3K and SREBP-1c may explain the defective regulation of miR-1 and miR-133a expression in response to insulin in muscle of type 2 diabetic patients. [3]
microRNAs act by lowering the expression of genes by binding to target sites in the 3' UTR of the mRNAs. Luo et al.. demonstrated that the HCN2 K+ channel gene contains a target of miR-133. [4] Yin et al.. showed that the Mps1 kinase gene in zebrafish is a target. [5] Boutz et al.. showed that nPTB (neuronal polypyrimidine tract-binding protein) is a target and likely contains two target sites for miR-133. [6] Xiao et al.. show that ether-a-go-go related gene (ERG) a K+ channel is a target of miR-133. [7]
miR-133 directly and negatively regulates NFATc4. [8] [9]
RhoA expression is negatively regulated by miR-133a in bronchial smooth muscles (BSM)and miR-133a downregulation causes an upregulation of RhoA, resulting in an augmentation of contraction and BSM hyperresponsiveness. [10]
BMP2 downregulates multiple mIRs, of which one, miR-133, directly inhibits Runx2, an early BMP response gene essential for bone formation. Although miR-133 is known to promote MEF-2-dependent myogenesis, it also inhibits Runx2-mediated osteogenesis. BMP2 controls bone cell determination by inducing miRNAs that target muscle genes but mainly by down-regulating multiple miRNAs that constitute an osteogenic program, thereby releasing from inhibition pathway components required for cell lineage commitment establish a mechanism for BMP morphogens to selectively induce a tissue-specific phenotype and suppress alternative lineages. [11]
Nicotine activates α7-nAChR and downregulates the levels of miR-133 and miR-590 leading to significant upregulation of expression of TGF-β1 and TGF-βRII at the protein level establishing miR-133 and miR-590 as repressors of TGF-β1 and TGF-βRII. [12]
miR-133 enhances myoblast proliferation by repressing serum response factor (SRF) [13]
mIR-133 suppresses SP1 expression [14]
In rats, miR-133b is expressed in retinal dopaminergicamacrine cell, and this expression is significantly increased during early stage during retinal degeneration. This overexpression leads to downregulation of the transcription factor PITX3. [15] miR-133a is down regulated in diabetic cardiomyopathy. [16]
miR-133 suppresses Prdm16 expression in skeletal muscle stem cells (satellite cells), which controls myogenic vs. brown adipogenic lineage determination in these cells. [17]
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