mir-133 is a type of
non-coding RNA called a
microRNA that was first experimentally characterised in mice.
Homologues have since been discovered in several other species including invertebrates such as the fruitfly ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Ch ...
''. 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.
Regulation
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.
Targets of miR-133
microRNAs act by lowering the expression of genes by binding to target sites in the
3' UTR
In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally ...
of the mRNAs. Luo ''et al.''. demonstrated that the
HCN2
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 is a protein that in humans is encoded by the ''HCN2'' gene.
Interactions
HCN2 has been shown to interact with HCN1 and HCN4.
Function
The function of the ...
K
+ channel gene contains a target of miR-133.
Yin ''et al.''. showed that the Mps1 kinase gene in zebrafish is a target.
Boutz ''et al.''. showed that
nPTB (neuronal polypyrimidine tract-binding protein) is a target and likely contains two target sites for miR-133.
Xiao ''et al.''. show that ether-a-go-go related gene (ERG) a K
+ channel is a target of miR-133.
miR-133 directly and negatively regulates NFATc4.
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.
downregulates multiple mIRs, of which one, miR-133, directly inhibits
Runx2
Runt-related transcription factor 2 (RUNX2) also known as core-binding factor subunit alpha-1 (CBF-alpha-1) is a protein that in humans is encoded by the ''RUNX2'' gene. RUNX2 is a key transcription factor associated with osteoblast differentia ...
, 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.
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.
miR-133 enhances myoblast proliferation by repressing serum response factor (SRF)
mIR-133 suppresses SP1 expression
In rats, miR-133b is expressed in retinal dopaminergic
amacrine cell
Amacrine cells are interneurons in the retina. They are named from the Greek roots ''a–'' ("non"), ''makr–'' ("long") and ''in–'' ("fiber"), because of their short neuronal processes. Amacrine cells are inhibitory neurons, and they proje ...
, and this expression is significantly increased during early stage during retinal degeneration. This overexpression leads to downregulation of the transcription factor
PITX3.
miR-133a is down regulated in diabetic cardiomyopathy.
miR-133 suppresses Prdm16 expression in skeletal muscle stem cells (satellite cells), which controls myogenic vs. brown adipogenic lineage determination in these cells.
References
Further reading
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External links
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miRBase entry for mir-133MicroRNA of the week at the miRNA blog
{{miRNA precursor families
MicroRNA
MicroRNA precursor families