Mir-199 microRNA precursor

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mir-199 microRNA precursor
RF00144.jpg
Predicted secondary structure and sequence conservation of mir-199
Identifiers
Symbolmir-199
Rfam RF00144
miRBase MI0000242
miRBase family MIPF0000040
Other data
RNA type Gene; miRNA
Domain(s) Eukaryota
GO GO:0035195 GO:0035068
SO 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]

Contents

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]

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.

The Let-7 microRNA precursor was identified from a study of developmental timing in C. elegans, and was later shown to be part of a much larger class of non-coding RNAs termed microRNAs. miR-98 microRNA precursor from human is a let-7 family member. Let-7 miRNAs have now been predicted or experimentally confirmed in a wide range of species (MIPF0000002). miRNAs are initially transcribed in long transcripts called primary miRNAs (pri-miRNAs), which are processed in the nucleus by Drosha and Pasha to hairpin structures of about 70 nucleotide. These precursors (pre-miRNAs) are exported to the cytoplasm by exportin5, where they are subsequently processed by the enzyme Dicer to a ~22 nucleotide mature miRNA. The involvement of Dicer in miRNA processing demonstrates a relationship with the phenomenon of RNA interference.

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-10 microRNA precursor family

The mir-10 microRNA precursor is a short non-coding RNA gene involved in gene regulation. It is part of an RNA gene family which contains mir-10, mir-51, mir-57, mir-99 and mir-100. mir-10, mir-99 and mir-100 have now been predicted or experimentally confirmed in a wide range of species. miR-51 and miR-57 have currently only been identified in the nematode Caenorhabditis elegans.

mir-17 microRNA precursor family

The miR-17 microRNA precursor family are a group of related small non-coding RNA genes called microRNAs that regulate gene expression. The microRNA precursor miR-17 family, includes miR-20a/b, miR-93, and miR-106a/b. With the exception of miR-93, these microRNAs are produced from several microRNA gene clusters, which apparently arose from a series of ancient evolutionary genetic duplication events, and also include members of the miR-19, and miR-25 families. These clusters are transcribed as long non-coding RNA transcripts that are processed to form ~70 nucleotide microRNA precursors, that are subsequently processed by the Dicer enzyme to give a ~22 nucleotide products. The mature microRNA products are thought to regulate expression levels of other genes through complementarity to the 3' UTR of specific target messenger RNA.

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.

The miR-34 microRNA precursor family are non-coding RNA molecules that, in mammals, give rise to three major mature miRNAs. The miR-34 family members were discovered computationally and later verified experimentally. The precursor miRNA stem-loop is processed in the cytoplasm of the cell, with the predominant miR-34 mature sequence excised from the 5' arm of the hairpin.

mir-92 microRNA precursor family

The miR-92 microRNAs are short single stranded non-protein coding RNA fragments initially discovered incorporated into an RNP complex with a proposed role of processing RNA molecules and further RNP assembly. Mir-92 has been mapped to the human genome as part of a larger cluster at chromosome 13q31.3, where it is 22 nucleotides in length but exists in the genome as part of a longer precursor sequence. There is an exact replica of the mir-92 precursor on the X chromosome. MicroRNAs are endogenous triggers of the RNAi pathway which involves several ribonucleic proteins (RNPs) dedicated to repressing mRNA molecules via translation inhibition and/or induction of mRNA cleavage. miRNAs are themselves matured from their long RNA precursors by ribonucleic proteins as part of a 2 step biogenesis mechanism involving RNA polymerase 2.

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-200

In molecular biology, the miR-200 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by binding and cleaving mRNAs or inhibiting translation. The miR-200 family contains miR-200a, miR-200b, miR-200c, miR-141, and miR-429. There is growing evidence to suggest that miR-200 microRNAs are involved in cancer metastasis.

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-210 microRNA

In molecular biology mir-210 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

miR-138

miR-138 is a family of microRNA precursors found in animals, including humans. MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The excised region or, mature product, of the miR-138 precursor is the microRNA mir-138.

miR-27 Family of microRNA precursors found in animals

miR-27 is a family of microRNA precursors found in animals, including humans. MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The excised region or, mature product, of the miR-27 precursor is the microRNA mir-27.

miR-214

miR-214 is a vertebrate-specific family of microRNA precursors. 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.

<span class="mw-page-title-main">MicroRNA 210</span>

MicroRNA 210 is a protein that in humans is encoded by the MIR210 gene.

References

  1. ↑ Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T (February 2003). "New microRNAs from mouse and human". RNA. 9 (2): 175–9. doi:10.1261/rna.2146903. PMC   1370382 . PMID   12554859.
  2. ↑ Houbaviy HB, Murray MF, Sharp PA (August 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 (February 2003). "Numerous microRNPs in neuronal cells containing novel microRNAs". RNA. 9 (2): 180–6. doi:10.1261/rna.2141503. PMC   1370383 . PMID   12554860.
  4. ↑ MIPF0000040
  5. ↑ Ambros V (December 2001). "microRNAs: tiny regulators with great potential". Cell. 107 (7): 823–6. doi: 10.1016/S0092-8674(01)00616-X . PMID   11779458. S2CID   14574186.
  6. 1 2 Desvignes, T; Postlethwait JH. 2013. Evolution of the miR199-214 cluster and vertebrate skeletal development. Submitted to RNA Biology.[ verification needed ]
  7. 1 2 Loebel DA, Tsoi B, Wong N, Tam PP (June 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 S, Chan WY (2012). "Flexible and versatile as a chameleon-sophisticated functions of microRNA-199a". International Journal of Molecular Sciences. 13 (7): 8449–66. doi:10.3390/ijms13078449. PMC   3430244 . PMID   22942713.
  9. ↑ Kim S, Lee UJ, Kim MN, Lee EJ, Kim JY, Lee MY, Choung S, Kim YJ, Choi YC (June 2008). "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. doi:10.1074/jbc.M800186200. PMID   18456660.
  10. ↑ Chen R, Alvero AB, Silasi DA, Kelly MG, Fest S, Visintin I, Leiser A, Schwartz PE, Rutherford T, Mor G (August 2008). "Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells". Oncogene. 27 (34): 4712–23. doi:10.1038/onc.2008.112. PMC   3041589 . PMID   18408758.
  11. ↑ Lee JW, Choi CH, Choi JJ, Park YA, Kim SJ, Hwang SY, Kim WY, Kim TJ, Lee JH, Kim BG, Bae DS (May 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 EA, Kong L, Bai XH, Luan Y, Liu CJ (April 2009). "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. doi:10.1074/jbc.M807709200. PMC   2670138 . PMID   19251704.
  13. ↑ Lee YB, Bantounas I, Lee DY, Phylactou L, Caldwell MA, Uney JB (January 2009). "Twist-1 regulates the miR-199a/214 cluster during development". Nucleic Acids Research. 37 (1): 123–8. doi:10.1093/nar/gkn920. PMC   2615617 . PMID   19029138.
  14. ↑ Burkardt DD, Rosenfeld JA, Helgeson ML, Angle B, Banks V, Smith WE, Gripp KW, Moline J, Moran RT, Niyazov DM, Stevens CA, Zackai E, Lebel RR, Ashley DG, Kramer N, Lachman RS, Graham JM (June 2011). "Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25". American Journal of Medical Genetics. Part A. 155A (6): 1336–51. doi:10.1002/ajmg.a.34049. PMC   3109510 . PMID   21548129.
  15. ↑ Yeligar S, Tsukamoto H, Kalra VK (October 2009). "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. doi:10.4049/jimmunol.0901084. PMC   3622549 . PMID   19783678.

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