Biology:mir-199 microRNA precursor
| mir-199 microRNA precursor | |
|---|---|
 Predicted secondary structure and sequence conservation of mir-199 | |
| Identifiers | |
| Symbol | mir-199 |
| Rfam | RF00144 |
| miRBase | MI0000242 |
| miRBase family | MIPF0000040 |
| Other data | |
| RNA type | Gene; miRNA |
| Domain(s) | Eukaryota |
| GO | 0035195 0035068 |
| SO | 0001244 |
| PDB structures | PDBe |
The miR-199 microRNA precursor is a short non-coding RNA gene involved in gene regulation. miR-199 genes have now been predicted or experimentally confirmed in mouse, human and a further 21 other species.[1][2][3][4] microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The mature products are thought to have regulatory roles through complementarity to mRNA.[5]
Origin and evolution of miR-199
miR-199 has been shown to be a vertebrate specific miR family that emerge at the origin of the vertebrate lineage [6] Three paralogs of miR-199 can usually be found in non-teleost vertebrate species and 4 to 5 copies in the teleost species. All miR-199 genes are located on opposite strand of orthologous intron of Dynamin genes. Within Dynamin3 gene (Dnm3), miR-199 is associated with miR-214 and both miRs are transcribed together as a common primary transcript, demonstrated in mouse, human and zebrafish.[7]
Targets and expression of miR-199
miR-199 has been shown to be implicated in a wide variety of cellular and developmental mechanisms such as various cancer development and progression, cardiomyocytes protection or skeletal formation.[8]
Using microarray and immunoblotting analyses it has been shown that miR-199a* targets the Met proto-oncogene.[9]
MicroRNA hsa-miR-199a is a regulator of IκB kinase-β (IKKβ) expression.[10]
Using TaqMan real-time quantitative PCR array methods, miRNA expression has been profiled. miR-199a, one of the most significantly overexpressed in invasive squamous cell carcinomas (ISCCs), was evaluated by transfecting cervical cancer cells (SiHa and ME-180) with anti-miR-199a oligonucleotides and the cell viability assessed. mirR-199a*, mir199a and mirR-199b were significantly overexpressed in ISCCs.[11]
Implication of miR-199 in skeletogenesis
miR-199, along with its cluster mate MiR-214, has been shown to be implicated in skeleton formation. In mice, miR-199 is expressed in perichondrial cells, periarticular chondrocytes, tracheal cartilage, limb mesenchyme, and most tissues in the upper and lower jaw.[7] In zebrafish, miR-199 is expressed in the developing notochord and in all tissues surrounding developing skeletal elements.[6] Comparative miRNA array led to the isolation of several Bone Morphogenic Protein 2 (BMP2)-responsive miRNAs. Among them, miR-199a* is of particular interest, because it was reported to be specifically expressed in the skeletal system and was shown to inhibit chondrogenesis by down-regulation of Smad1, a major regulator of bone and cartilage formation and development.[12] Also, Twist-1, which is a major actor in skeleton formation, regulates miR-199 and miR-214 cluster expression in mouse.[13] Furthermore, miR199-214 cluster deletion in mouse lead to skeletal development abnormalities including craniofacial defects, neural arch and spinous processes malformations, and osteopenia.[14]
Clinical relevance of miR-199
Alcoholic liver disease is a common medical consequence of long-term excessive alcohol use. Activation of hypoxia-Inducible Factor-1α (HIF-1α) is an indicator of hypoxia. Endothelin-1 (ET-1) is a protein that constricts blood vessels and raises blood pressure. It has been shown that ethanol-induced miR-199 down-regulation may contribute to augmented HIF-1α and ET-1 expression.[15]
References
- ↑ "New microRNAs from mouse and human". RNA 9 (2): 175–9. February 2003. doi:10.1261/rna.2146903. PMID 12554859.
- ↑ "Embryonic stem cell-specific MicroRNAs". Developmental Cell 5 (2): 351–8. August 2003. doi:10.1016/S1534-5807(03)00227-2. PMID 12919684.
- ↑ "Numerous microRNPs in neuronal cells containing novel microRNAs". RNA 9 (2): 180–6. February 2003. doi:10.1261/rna.2141503. PMID 12554860.
- ↑ MIPF0000040
- ↑ "microRNAs: tiny regulators with great potential". Cell 107 (7): 823–6. December 2001. doi:10.1016/S0092-8674(01)00616-X. PMID 11779458.
- ↑ 6.0 6.1 Desvignes, T; Postlethwait JH. 2013. Evolution of the miR199-214 cluster and vertebrate skeletal development. Submitted to RNA Biology.[verification needed]
- ↑ 7.0 7.1 "A conserved noncoding intronic transcript at the mouse Dnm3 locus". Genomics 85 (6): 782–9. June 2005. doi:10.1016/j.ygeno.2005.02.001. PMID 15885504.
- ↑ "Flexible and versatile as a chameleon-sophisticated functions of microRNA-199a". International Journal of Molecular Sciences 13 (7): 8449–66. 2012. doi:10.3390/ijms13078449. PMID 22942713.
- ↑ "MicroRNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2)". The Journal of Biological Chemistry 283 (26): 18158–66. June 2008. doi:10.1074/jbc.M800186200. PMID 18456660.
- ↑ "Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells". Oncogene 27 (34): 4712–23. August 2008. doi:10.1038/onc.2008.112. PMID 18408758.
- ↑ "Altered MicroRNA expression in cervical carcinomas". Clinical Cancer Research 14 (9): 2535–42. May 2008. doi:10.1158/1078-0432.CCR-07-1231. PMID 18451214.
- ↑ "miR-199a, a bone morphogenic protein 2-responsive MicroRNA, regulates chondrogenesis via direct targeting to Smad1". The Journal of Biological Chemistry 284 (17): 11326–35. April 2009. doi:10.1074/jbc.M807709200. PMID 19251704.
- ↑ "Twist-1 regulates the miR-199a/214 cluster during development". Nucleic Acids Research 37 (1): 123–8. January 2009. doi:10.1093/nar/gkn920. PMID 19029138.
- ↑ "Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25". American Journal of Medical Genetics. Part A 155A (6): 1336–51. June 2011. doi:10.1002/ajmg.a.34049. PMID 21548129.
- ↑ "Ethanol-induced expression of ET-1 and ET-BR in liver sinusoidal endothelial cells and human endothelial cells involves hypoxia-inducible factor-1alpha and microrNA-199". Journal of Immunology 183 (8): 5232–43. October 2009. doi:10.4049/jimmunol.0901084. PMID 19783678.
Further reading
- "Differential expression of microRNAs in early-stage neoplastic transformation in the lungs of F344 rats chronically treated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone". Carcinogenesis 29 (12): 2394–9. December 2008. doi:10.1093/carcin/bgn209. PMID 18780894.
- "Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion". Molecular Cancer 9: 227. August 2010. doi:10.1186/1476-4598-9-227. PMID 20799954.
- "Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210". Antiviral Research 88 (2): 169–75. November 2010. doi:10.1016/j.antiviral.2010.08.008. PMID 20728471.
- "MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells". Cancer Research 70 (12): 5184–93. June 2010. doi:10.1158/0008-5472.CAN-10-0145. PMID 20501828.
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