mir-199 microRNA precursor

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mir-199 microRNA precursor
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[edit]

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[edit]

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[edit]

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, whichis 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[edit]

Alcoholic liver disease is a common medical consequence of chronic alcohol abuse. 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]


  1. ^ Lagos-Quintana, M.; Rauhut, R; Meyer, J; Borkhardt, A; Tuschl, T (2003). "New microRNAs from mouse and human". RNA. 9 (2): 175–9. doi:10.1261/rna.2146903. PMC 1370382Freely accessible. PMID 12554859. 
  2. ^ Houbaviy, Hristo B; Murray, Michael F; Sharp, Phillip A (2003). "Embryonic Stem Cell-Specific MicroRNAs". Developmental Cell. 5 (2): 351–8. doi:10.1016/S1534-5807(03)00227-2. PMID 12919684. 
  3. ^ Dostie, J.; Mourelatos, Z; Yang, M; Sharma, A; Dreyfuss, G (2003). "Numerous microRNPs in neuronal cells containing novel microRNAs". RNA. 9 (2): 180–6. doi:10.1261/rna.2141503. PMC 1370383Freely accessible. PMID 12554860. 
  4. ^ MIPF0000040[permanent dead link]
  5. ^ Ambros, Victor (2001). "MicroRNAs". Cell. 107 (7): 823–6. doi:10.1016/S0092-8674(01)00616-X. PMID 11779458. 
  6. ^ a b Desvignes, T; Postlethwait JH. 2013. Evolution of the miR199-214 cluster and vertebrate skeletal development. Submitted to RNA Biology.[verification needed]
  7. ^ a b Loebel, David A.F.; Tsoi, Bonny; Wong, Nicole; Tam, Patrick P.L. (2005). "A conserved noncoding intronic transcript at the mouse Dnm3 locus". Genomics. 85 (6): 782–9. doi:10.1016/j.ygeno.2005.02.001. PMID 15885504. 
  8. ^ Gu, Shen; Chan, Wai-Yee (2012). "Flexible and Versatile as a Chameleon—Sophisticated Functions of microRNA-199a". International Journal of Molecular Sciences. 13 (12): 8449–66. doi:10.3390/ijms13078449. PMC 3430244Freely accessible. PMID 22942713. 
  9. ^ Kim, Seonhoe; Lee, Ui Jin; Kim, Mi Na; Lee, Eun-Ju; Kim, Ji Young; Lee, Mi Young; Choung, Sorim; Kim, Young Joo; Choi, Young-Chul (2008). "MicroRNA miR-199a* Regulates the MET Proto-oncogene and the Downstream Extracellular Signal-regulated Kinase 2 (ERK2)". Journal of Biological Chemistry. 283 (26): 18158–66. doi:10.1074/jbc.M800186200. PMID 18456660. 
  10. ^ Chen, R; Alvero, A B; Silasi, D A; Kelly, M G; Fest, S; Visintin, I; Leiser, A; Schwartz, P E; Rutherford, T; Mor, G (2008). "Regulation of IKKβ by miR-199a affects NF-κB activity in ovarian cancer cells". Oncogene. 27 (34): 4712–23. doi:10.1038/onc.2008.112. PMC 3041589Freely accessible. PMID 18408758. 
  11. ^ Lee, Jeong-Won; Choi, Chel Hun; Choi, Jung-Joo; Park, Young-Ae; Kim, Seung-Jun; Hwang, Seung Yong; Kim, Woo Young; Kim, Tae-Joong; Lee, Je-Ho; Kim, Byoung-Gie; Bae, Duk-Soo (2008). "Altered MicroRNA Expression in Cervical Carcinomas". Clinical Cancer Research. 14 (9): 2535–42. doi:10.1158/1078-0432.CCR-07-1231. PMID 18451214. 
  12. ^ Lin, Edward A.; Kong, Li; Bai, Xiao-Hui; Luan, Yi; Liu, Chuan-ju (2008). "MiR-199a*, a Bone Morphogenic Protein 2-responsive MicroRNA, Regulates Chondrogenesis via Direct Targeting to Smad1". Journal of Biological Chemistry. 284 (17): 11326–35. doi:10.1074/jbc.M807709200. PMC 2670138Freely accessible. PMID 19251704. 
  13. ^ Lee, Youn-Bok; Bantounas, Ioannis; Lee, Do-Young; Phylactou, Leonidas; Caldwell, Maeve A.; Uney, James B. (2008). "Twist-1 regulates the miR-199a/214 cluster during development". Nucleic Acids Research. 37 (1): 123–8. doi:10.1093/nar/gkn920. PMC 2615617Freely accessible. PMID 19029138. 
  14. ^ Burkardt, Deepika D'Cunha; Rosenfeld, Jill A.; Helgeson, Maria L.; Angle, Brad; Banks, Valerie; Smith, Wendy E.; Gripp, Karen W.; Moline, Jessica; Moran, Rocio T.; Niyazov, Dmitriy M.; Stevens, Cathy A.; Zackai, Elaine; Lebel, Robert Roger; Ashley, Douglas G.; Kramer, Nancy; Lachman, Ralph S.; Graham, John M. (2011). "Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25". American Journal of Medical Genetics Part A. 155 (6): 1336–51. doi:10.1002/ajmg.a.34049. PMC 3109510Freely accessible. PMID 21548129. 
  15. ^ Yeligar, S.; Tsukamoto, H.; Kalra, V. K. (2009). "Ethanol-Induced Expression of ET-1 and ET-BR in Liver Sinusoidal Endothelial Cells and Human Endothelial Cells Involves Hypoxia-Inducible Factor-1 and MicroRNA-199". The Journal of Immunology. 183 (8): 5232–43. doi:10.4049/jimmunol.0901084. PMC 3622549Freely accessible. PMID 19783678. 

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