Mir-433

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mir-433
MiR-433 secondary structure.png
miR-433 microRNA secondary structure and sequence conservation
Identifiers
Symbolmir-433
Rfam RF00748
miRBase family MIPF0000177
NCBI Gene 574034
HGNC 32026
OMIM 611711
Other data
RNA type microRNA
Domain(s) Eukaryota; Eutheria;
PDB structures PDBe

In molecular biology, mir-433 is a short non-coding RNA molecule. MicroRNAs (miRNAs) function as posttranscriptional regulators of expression levels of other genes by several mechanisms. [1] They play roles in development, metabolism and carcinogenesis. [2]

Contents

Genomic structure and regulation

Mir-433 is one of 21 miRNAs found in a cluster on chromosome 12. [3]

The 3′ coding region of mir-433 is also the promoter of the neighbouring miRNA gene: mir-127. [3] The two genes overlap and are transcribed in the same orientation. [2] This is a method by which genetic information can be stored in a compact and efficient way. [2]

Mir-433, along with the other twenty genes in the cluster, is upregulated in small heterodimer partner (SHP) homozygous knockout mice. [3] 

SHP is a nuclear receptor known to repress transcription, and it has a role in some metabolic diseases. Conversely, the transcription of mir-433 has been shown to be activated by estrogen related receptor (ERR). [3]

Mir-433 is highly conserved across species, being 95% similar in the human, chimpanzee, horse, dog, monkey, rat, cow and mouse. [4] The distance between mir-433 and mir-127 was also similar across these species; as was the positioning of transcription factor binding motifs, including that for ERR. This indicates that the gene regulation, as well as the primary sequence, is conserved across these mammalian species.

It is also suggested that mir-433 and mir-127 are likely to have originated from a common ancestral gene. [4]

Disease association

Levels of mir-433 have been found to be elevated in gastric carcinoma, by investigation with miRNA gene microarrays. Mir-433 regulates the expression of GRB2, a known tumour-associated protein, which may be the explanation for this association. [5]

No such association was found between mir-433 variation and Parkinson's disease [6] despite the fact that variation in the region of the FGF20 gene which binds to mir-433, is associated with Parkinson's disease.

Mir-433 has also been associated with a dominantly inherited form of x linked chondrodysplasia. [7] Mir-433 normally downregulates the expression of HDAC6. A single nucleotide polymorphism (SNP) in the 3′ untranslated region (UTR) of HDAC6 was found to segregate with the chondrodysplasia. This SNP removes the ability of mir-433 to downregulate HDAC6, resulting in its overexpression. Consequently, there is reduced acetylation of its target, alpha tubulin, causing disease. [7]

See also

Related Research Articles

microRNA Small non-coding ribonucleic acid molecule

MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in mRNA molecules, then gene silence said mRNA molecules by one or more of the following processes:

  1. Cleavage of mRNA strand into two pieces,
  2. Destabilization of mRNA by shortening its poly(A) tail, or
  3. Translation of mRNA into proteins.

Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. Gene silencing can occur during either transcription or translation and is often used in research. In particular, methods used to silence genes are being increasingly used to produce therapeutics to combat cancer and other diseases, such as infectious diseases and neurodegenerative disorders.

<span class="mw-page-title-main">Regulation of gene expression</span> Modifying mechanisms used by cells to increase or decrease the production of specific gene products

Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products. Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.

mir-9/mir-79 microRNA precursor family

The miR-9 microRNA, is a short non-coding RNA gene involved in gene regulation. The mature ~21nt miRNAs are processed from hairpin precursor sequences by the Dicer enzyme. The dominant mature miRNA sequence is processed from the 5' arm of the mir-9 precursor, and from the 3' arm of the mir-79 precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. In vertebrates, miR-9 is highly expressed in the brain, and is suggested to regulate neuronal differentiation. A number of specific targets of miR-9 have been proposed, including the transcription factor REST and its partner CoREST.

mir-133 microRNA precursor family

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. 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.

mir-181 microRNA precursor

In molecular biology miR-181 microRNA precursor is a small non-coding RNA molecule. MicroRNAs (miRNAs) are transcribed as ~70 nucleotide precursors and subsequently processed by the RNase-III type enzyme Dicer to give a ~22 nucleotide mature product. In this case the mature sequence comes from the 5' arm of the precursor. They target and modulate protein expression by inhibiting translation and / or inducing degradation of target messenger RNAs. This new class of genes has recently been shown to play a central role in malignant transformation. miRNA are downregulated in many tumors and thus appear to function as tumor suppressor genes. The mature products miR-181a, miR-181b, miR-181c or miR-181d are thought to have regulatory roles at posttranscriptional level, through complementarity to target mRNAs. miR-181 which has been predicted or experimentally confirmed in a wide number of vertebrate species as rat, zebrafish, and in the pufferfish.

mir-19 microRNA precursor family

There are 89 known sequences today in the microRNA 19 (miR-19) family but it will change quickly. They are found in a large number of vertebrate species. The miR-19 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. Within the human and mouse genome there are three copies of this microRNA that are processed from multiple predicted precursor hairpins:

mir-1 microRNA precursor family

The miR-1 microRNA precursor is a small micro RNA that regulates its target protein's expression in the cell. microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give products at ~22 nucleotides. In this case the mature sequence comes from the 3' arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. In humans there are two distinct microRNAs that share an identical mature sequence, and these are called miR-1-1 and miR-1-2.

mir-219 microRNA precursor family

In molecular biology, the microRNA miR-219 was predicted in vertebrates by conservation between human, mouse and pufferfish and cloned in pufferfish. It was later predicted and confirmed experimentally in Drosophila. Homologs of miR-219 have since been predicted or experimentally confirmed in a wide range of species, including the platyhelminth Schmidtea mediterranea, several arthropod species and a wide range of vertebrates. The hairpin precursors are predicted based on base pairing and cross-species conservation; their extents are not known. In this case, the mature sequence is excised from the 5' arm of the hairpin.

mir-7 microRNA precursor

This family represents the microRNA (miRNA) precursor mir-7. This miRNA has been predicted or experimentally confirmed in a wide range of species. miRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. In this case the mature sequence comes from the 5' arm of the precursor. The extents of the hairpin precursors are not generally known and are estimated based on hairpin prediction. The involvement of Dicer in miRNA processing suggests a relationship with the phenomenon of RNA interference.

mIRN21 Non-coding RNA in the species Homo sapiens

microRNA 21 also known as hsa-mir-21 or miRNA21 is a mammalian microRNA that is encoded by the MIR21 gene.

mir-96 microRNA

miR-96 microRNA precursor is a small non-coding RNA that regulates gene expression. microRNAs are transcribed as ~80 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~23 nucleotide products. In this case the mature sequence comes from the 5′ arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA.

miR-155 Non-coding RNA in the species Homo sapiens

MiR-155 is a microRNA that in humans is encoded by the MIR155 host gene or MIR155HG. MiR-155 plays a role in various physiological and pathological processes. Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and enhance the progression of cardiovascular diseases.

mir-126

In molecular biology mir-126 is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several pre- and post-transcription mechanisms.

mir-127

mir-127 microRNA is a short non-coding RNA molecule with interesting overlapping gene structure. miR-127 functions to regulate the expression levels of genes involved in lung development, placental formation and apoptosis. Aberrant expression of miR-127 has been linked to different cancers.

mir-143 RNA molecule

In molecular biology mir-143 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. mir–143 is highly conserved in vertebrates. mir-143 is thought be involved in cardiac morphogenesis but has also been implicated in cancer.

mir-22

In molecular biology mir-22 microRNA is a short RNA molecule. MicroRNAs are an abundant class of molecules, approximately 22 nucleotides in length, which can post-transcriptionally regulate gene expression by binding to the 3' UTR of mRNAs expressed in a cell.

miR-296

miR-296 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.

lsy-6 microRNA belongs to the class of miRNAs; these function to regulate the expression levels of other genes by several mechanisms. lsy-6 is a short non-coding RNA molecule and the first miRNA identified as having a role in nervous system development. It regulates left-right neuronal asymmetry in the nematode worm Caenorhabditis elegans.

In molecular biology mir-153 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

References

  1. ↑ Cullen BR (December 2004). "Transcription and processing of human microRNA precursors". Mol. Cell. 16 (6): 861–865. doi: 10.1016/j.molcel.2004.12.002 . PMID   15610730.
  2. 1 2 3 Song G, Wang L (2008). Volff J (ed.). "MiR-433 and miR-127 arise from independent overlapping primary transcripts encoded by the miR-433-127 locus". PLOS ONE. 3 (10): e3574. doi: 10.1371/journal.pone.0003574 . PMC   2570487 . PMID   18974780.
  3. 1 2 3 4 Song G, Wang L (2008). "Transcriptional mechanism for the paired miR-433 and miR-127 genes by nuclear receptors SHP and ERRgamma". Nucleic Acids Res. 36 (18): 5727–5735. doi:10.1093/nar/gkn567. PMC   2566885 . PMID   18776219.
  4. 1 2 Song G, Wang L (2009). Tora L (ed.). "A conserved gene structure and expression regulation of miR-433 and miR-127 in mammals". PLOS ONE. 4 (11): e7829. doi: 10.1371/journal.pone.0007829 . PMC   2778354 . PMID   19946636.
  5. ↑ Luo H, Zhang H, Zhang Z, Zhang X, Ning B, Guo J, Nie N, Liu B, Wu X (2009). "Down-regulated miR-9 and miR-433 in human gastric carcinoma". J Exp Clin Cancer Res. 28 (1): 82. doi: 10.1186/1756-9966-28-82 . PMC   2739520 . PMID   19531230.
  6. ↑ de Mena L, Cardo LF, Coto E, Miar A, DÃaz M, Corao AI, Alonso B, Ribacoba R, Salvador C, Menéndez M, MorÃs G, Alvarez V (2010). "FGF20 rs12720208 SNP and microRNA-433 variation: no association with Parkinson's disease in Spanish patients". Neurosci Lett. 479 (1): 22–25. doi:10.1016/j.neulet.2010.05.019. PMID   20471450. S2CID   15904325.
  7. 1 2 Simon D, Laloo B, Barillot M, Barnetche T, Blanchard C, Rooryck C, Marche M, Burgelin I, Coupry I, Chassaing N, Gilbert-Dussardier B, Lacombe D, Grosset C, Arveiler B (2010). "A mutation in the 3′-UTR of the HDAC6 gene abolishing the post-transcriptional regulation mediated by hsa-miR-433 is linked to a new form of dominant X-linked chondrodysplasia". Hum Mol Genet. 19 (10): 2015–2027. doi: 10.1093/hmg/ddq083 . PMID   20181727.
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