|mir-19 microRNA precursor family|
|RNA type||Gene; miRNA|
There maybe 89 known sequences today in the microRNA 19 (miR-19) familly but it will change too fast. They are found into 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-19a on chromosome 14 (MI0000688)
- * miR-19b-1 on chromosome 14 (MI0000718)
- * miR-19b-2 on chromosome X (MI0000546)
- * miR-19a on chromosome 13 (MI0000073)
- * miR-19b-1 on chromosome 13 (MI0000074)
- * miR-19b-2 on chromosome X (MI000075).
- 1 Origins
- 2 Expression
- 3 miR-19a/b roles
- 4 miR-19a Roles
- 5 miR-19b Roles
- 6 References
- 7 Further reading
- 8 External links
The presence of miR-19 has been detected in a diverse range of vertebrate animals including green anole (Anolis carolinensis), primates (gorilla, human,…), cattle (Bos taurus), dog, chinese hamster (Cricetulus griseus), zebrafish (Danio rerio), horse (Equus caballus), Takifugu rubripes,Tetraodon nigroviridis, chicken (Gallus gallus), gray short-tailed opossum (Monodelphis domestica), platypus (Ornithorhynchus anatinus), Japanese medaka (Oryzias latipes), Xenopus laevis (frog), Tasmanian devil (Sarcophilus harrisii), pig (Sus scrofa) and Zebra Finch (Taeniopygia guttata).
In some of these species the presence of miR-19 has been shown experimentally, in others the genes encoding miR-19 have been predicted computationally.
MicroRNA from miR-19 family can be expressed from:
- * T-cell acute lymphoblastic leukemia 
- * B-cell lymphomas 
- * cell lines 
- * Cerebellum 
- * Purkinje cells 
- * HeLa cells 
They finaly have tissues-specific miRNA expression. These microRNA are considered as oncogenes which improve proliferation, inhibits apoptosis and induce tumor angiogenesis.
Those miRNA are context-specifics and they have different rôles depending on the place they are.
Acute lymphoblastic leukemia
Ectopic expression of miR-19 represses CYLD expression, while miR-19 inhibitor treatment induces CYLD protein expression and decreases NF-kB expression in the downstream signaling pathway. Thus, miR-19, CYLD and NF-kB form a regulatory feedforward loop, which provides new clues for sustained activation of NF-kB in T-cell acute lymphoblastic leukemia.
MiR-19 is sufficient to induce T-cell lymphoblastic leukemia activating Notch1 and accelerate the disease. It's targets are:
- * Bim (Bcl2L11) gene
- * AMP-activated kinase (Prkaa1) gene
- * E2F1 gene
- * the tumour suppressor phosphatases PTEN
- * PP2A (Ppp2r5e) gene
- * Dock5 protein
Primary central nervous system lymphoma
Baraniskin and al. study show that miR-21, miR-19, and miR-92a levels in cerebrospinal fluid (CSF) seems to be good biomarkers to diagnose a Primary central nervous system lymphoma (PCNSL). They also demonstrate that miRNAs in plasma are in a resistant form to intrinsic RNase activity, and there is a low RNase activity in the CSF.
MiR-19 has been identified as a key responsible for the oncogenic activity, reducing the tumor suppressor gene PTEN expression and activating AKT/mTOR pathway. This cluster might be important regulator on cancer and aging.
Mu and al. demonstrated that the expression of endogenous miR-17-92 is required to suppress apoptosis in Myc-driven B-cell lymphomas. More specificly, miR-19a and miR-19b are required and sufficient to recapitulate the oncogenic properties of the entire cluster. Using prediction algorithms, they found miR-19 targets to the prosurvival functions:
In the cell response to stress, the most important is the post-transcriptional control of the important gene expression to cell survival and apoptosis. MiR-19 regulates the Ras homolog B (RhoB) expression in keratinocytes after ultraviolet (UV) radiation exposition. This phenomenon needs the binding of human antigen R (HuR) to the rhoB mRNA 3'-untranslated region. In this case, HuR positively act on miRNA action. The interaction between HuR and miR-19 with rhoB is lost under UV tratment. Here, miR-19, linked to RhoB, act like a protector against keratinocyte apoptosis. A 52-nucleotide-long sequence of the rhoB 3'-UTR spanning bases 818–870, containing the miR-19 and the HuR binding site was sufficient for UV regulation. This event is UV dependant!
Multiple Myeloma (MM)
One study on multiple myeloma patients permited to identifyed a selective up-regulation of miR-32 and the miR-17-92 cluster. MiR-19a and miR-19b were shown to down regulate SOCS-1 expression (a specific gene that inhibates IL-6 growth signaling). Therefore, miR-17-92 with miR-21, inhibits apoptosis and promotes cell survival.
In this case, miR-17-92 cluster promotes retinoblastoma due to loss of Rb family members. The mouse retinal development need miR-17-92 overexpresson with Rb and p107 deletion, but it occured frequent emergence of retinoblastoma and metastasis to the brain.
Here, the cluster oncogenic function is not mediated by a miR-19/PTEN axis toward apoptosis suppression like in lymphoma or in leukemia models. MiR-17-92 increase the proliferative capacity of Rb/p107-deficient in retinal cells.
Moreover, the Rb family members deletion led to compensatory up-regulation of the cyclin-dependent kinase inhibitor p21Cip1.
Finaly, the cluster overexpression counteracted p21Cip1 up-regulation, promotes proliferation and drove retinoblastoma formation.
Role in normal development of heart, lungs and immune system
Scientists observed that the loss of function of miR-17-92 cluster is induced in smaller embryos and postnatal death. The specific role of this cluster in heart and lung development remain unclear, but the observations described above show that these miRNAs are normally highly expressed in embryonic lung and decrease with maturity. Moreover, transgenic expression of these miRNAs specifically in lung epithelium results in severe developmental defects with enhanced proliferation and inhibition of differentiation of epithelial cells.
Furthermore, mouse hematopoiesis occurring in the absence of miR-17-92 leads to an isolated defect in B cell development.
Role in the endothelial differenciation of stem cells
The miR-17-92 cluster containing miR-19 miRNA family is also involved into control endothelial cell functions and nerovascularization. MiRNA cluster (miR-17, miR-18, miR-19 and miR-20) increased during the induction of endothelial cell differenciation in embryonic stem cells (tested on murine) or induce pluripotent stem cells. Eventhough this cluster regulates vascular integrity and angiogenesis, none of each members has a significant impact on the endothelial differenciation of pluripotent stem cells.
Spinocerebellar ataxia type 1
It has been showing that the 3' UTR of the ATXN1 gene contains 3 target sites for miR-19, and this microRNA shows moderate down regulation of reporter genes containing the ATXN1 3' UTR. Furthermore, it directly bind to the ATXN1 3´UTR to suppress the translation of ATXN1. ATXN1 is also regulated by miR-101, and miR-130.
MiR-19 regulates tissue factor expression at a post-transcriptional level in breast cancer cells, providing a molecular basis for the selective expression of the tissue factor gene. Thanks to bioinformatics anlyses, scientists predicted microRNA-Binding sites for miR-19, miR-20 and miR-106b in the 3'-UTR tissue factor transcript. Experiments confirmed that it negatively regulates gene expression in MCF-7 cells, and overexpression of miR-19 downregulates tissue factor expression in MDA-MB-231 cells (Human breast cancer cell lines). The main action of miR-19 seems to inhibit protein translation of the tissue factor gene in less invasive breast cancer cells.
MiR-19 also takes part in inflammatory responses enhancing or repressing pro-inflammatory mediators expression. It positively regulates Toll-like receptor sigaling with Dicer1 deletion and miRNA depletion. MiR-19b is an important protagonist in this phenomenon, regulating positively NF-kB activity. MiRNA depletion inhibits cytokines production by NF-kB. This indicates that miRNA control of NF-kB signaling repressors thanks to its relief. Some important regulators of NF-kB signaling (like A20 (Tnfaip3), Cyld, and Cezanne (Otud7b)) is targeted by the miR-17-92 cluster.
Moreover, mir-19 targets some members of the Tnfaip3-ubiquitin editing complex (Tnfaip3/Itch/Tnip1/Rnf11). MiR-19 directly involved in the modulation of several NF-kB signaling negative regulators expression, indicating an important role for Rnf11 in the effect of miR-19b on NF-kB signaling.
Finaly, miR-19b exacerbates the cells crucial inflammatory activation in rheumatoid arthritis disease.
- Lagos-Quintana, M (2001). "Identification of novel genes coding for small expressed RNAs". Science. 294 (5543): 853–858. PMID 11679670. doi:10.1126/science.1064921. Unknown parameter
- Mourelatos, Z (2002). "miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs". Genes Dev. 16 (6): 720–728. PMC . PMID 11914277. doi:10.1101/gad.974702. Unknown parameter
- Houbaviy, HB (2003). "Embryonic stem cell-specific MicroRNAs". Dev Cell. 5 (2): 351–358. PMID 12919684. doi:10.1016/S1534-5807(03)00227-2. Unknown parameter
- Landgraf, P (2007). "A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing". Cell. 129(7): 1401–1414. PMID 17604727. doi:10.1016 Check
|doi=value (help). Unknown parameter
- Lyson TR, Sperling EA, Heimberg AM and al. (2012). "MicroRNAs support a turtle + lizard clade". Biol Lett. 8 (1): 104–7. PMID 21775315. doi:10.1098/rsbl.2011.0477.
- Berezikov E, Guryev V, van de Belt J and al. (2005). "Phylogenetic shadowing and computational identification of human microRNA genes". Cell. 120 (1): 21–4. PMID 15652478.
- Lui WO, Pourmand N, Patterson BK and al. (2007). "Patterns of known and novel small RNAs in human cervical cancer". Cancer Res. 67 (13): 6031–43. PMID 17616659.
- Gu Z, Eleswarapu S, Jiang H (2007). "Identification and characterization of microRNAs from the bovine adipose tissue and mammary gland". FEBS Lett. 581 (5): 981–8. PMID 17306260.
- Friedländer MR, Chen W, Adamidi C and al. (2008). "Discovering microRNAs from deep sequencing data using miRDeep". Nat Biotechnol. 26 (4): 407–15. PMID 18392026. doi:10.1038/nbt1394.
- Hackl M, Jakobi T, Blom J and al. (2011). "Next-generation sequencing of the Chinese hamster ovary microRNA transcriptome: Identification, annotation and profiling of microRNAs as targets for cellular engineering". J Biotechnol. 153 (1-2): 62–75. PMID 21392545. doi:10.1016/j.jbiotec.2011.02.011.
- Chen PY, Manninga H, Slanchev K and al. (2005). "The developmental miRNA profiles of zebrafish as determined by small RNA cloning". Genes Dev. 19 (11): 1288–93. PMID 15937218. doi:10.1101/gad.1310605.
- Zhou M, Wang Q, Sun J and al. (2009). "In silico detection and characteristics of novel microRNA genes in the Equus caballus genome using an integrated ab initio and comparative genomic approach". Genomics. 94 (2): 125–31. PMID 19406225. doi:10.1016/j.ygeno.2009.04.006.
- International Chicken Genome Sequencing Consortium (2004). "Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution". Nature. 432 (7018): 695–716. PMID 15592404.
- Yao Y, Zhao Y, Xu H and al. (2008). "MicroRNA profile of Marek's disease virus-transformed T-cell line MSB-1: predominance of virus-encoded microRNAs". J Virol. 82 (8): 4007–15. PMID 18256158. doi:10.1128/JVI.02659-07.
- Devor EJ, Samollow PB (2008). "In vitro and in silico annotation of conserved and nonconserved microRNAs in the genome of the marsupial Monodelphis domestica". J Hered. 99 (1): 66–72. PMID 17965199.
- Murchison EP, Kheradpour P, Sachidanandam R and al. (2008). "Conservation of small RNA pathways in platypus". Genome Res. 18 (6): 995–1004. PMID 18463306. doi:10.1101/gr.073056.107.
- Li SC, Chan WC, Ho MR and al. (2010). "Discovery and characterization of medaka miRNA genes by next generation sequencing platform". BMC Genomics. PMID 21143817. doi:10.1186/1471-2164-11-S4-S8.
- Watanabe T, Takeda A, Mise K and al. (2005). "Stage-specific expression of microRNAs during Xenopus development". FEBS Lett. 579 (2): 318–24. PMID 15642338.
- Murchison EP, Tovar C, Hsu A and al. (2010). "The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer". Science. 327 (5961): 84–7. PMID 20044575. doi:10.1126/science.1180616.
- Wernersson R, Schierup MH, Jørgensen FG and al. (2005). "Pigs in sequence space: a 0.66X coverage pig genome survey based on shotgun sequencing". BMC Genomics: 6:70. PMID 15885146.
- Warren WC, Clayton DF, Ellegren H and al. (2010). "The genome of a songbird". Nature. 464 (7289): 757–62. PMID 20360741. doi:10.1038/nature08819.
- Huashan Ye, Xiaowen Liu, Meng Lv, Yuliang Wu, Shuzhen Kuang, Jing Gong, Ping Yuan, Zhaodong Zhong, Qiubai Li, Haibo Jia, Jun Sun, Zhichao Chen and An-Yuan Guo (2012). "MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia". Nucleic Acids Research. 40.
- Ping Mu, Yoon-Chi Han, Doron Betel, Evelyn Yao, Massimo Squatrito, Paul Ogrodowski, Elisa de Stanchina, Aleco D’Andrea, Chris Sander, Andrea Ventura (2009). "Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced B-cell lymphomas". Genes Dev. 23 (24): 2806–11. PMC . PMID 20008931. doi:10.1101/gad.1872909.
- Lee Y, Samaco RC, Gatchel JR, Thaller C, Orr HT, Zoghbi HY (2008). "miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis". Nat. Neurosci. 11 (10): 1137–9. PMC . PMID 18758459. doi:10.1038/nn.2183. Unknown parameter
- Alexander Baraniskin, Jan Kuhnhenn, Uwe Schlegel, Andrew Chan, Martina Deckert, Ralf Gold, Abdelouahid Maghnouj, Hannah Zöllner, Anke Reinacher-Schick, Wolff Schmiegel, Stephan A. Hahn, Roland Schroers (2011). "Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system". Blood. 117: 3140–3146. PMID 21200023. doi:10.1182/blood-2010-09-308684.
- Michael P. Gantier, H. James Stunden, Claire E. McCoy, Mark A. Behlke, Die Wang, Maria Kaparakis-Liaskos, Soroush T. Sarvestani, Yuan H. Yang, Dakang Xu, Sinéad C. Corr, Eric F. Morand, Bryan R. G. Williams (2012). "A miR-19 regulon that controls NF-iB signaling". Nucleic Acids Research. 40 (16): 8048–8058. PMC . doi:10.1093/nar/gks521.
- Xiaoxi Zhang, Haijun Yu, Jessica R. Lou, Jie Zheng, Hua Zhu, Narcis-Ioan Popescu, Florea Lupu, Stuart E. Lind, and Wei-Qun Ding (2011). "MicroRNA-19 (miR-19) Regulates Tissue Factor Expression in Breast Cancer Cells". The journal of Biological chemistry. 286: 1429–1435. PMC . PMID 21059650. doi:10.1074/jbc.M110.146530.
- Konstantinos J. Mavrakis1, Andrew L. Wolfe, Elisa Oricchio1, Teresa Palomero and al. (2011). "Genome-wide RNAi screen identifies miR-19 targets in Notchinduced acute T-cell leukaemia (T-ALL)". Nat Cell Biol. 12 (4): 372–379. PMC . PMID 20190740. doi:10.1038/ncb2037.
- Konstantinos J. Mavrakis and Hans-Guido Wendel (2010). "TargetScreen: an unbiased approach to identify functionally important microRNA targets". Cell Cycle. 9 (11): 2080–4. PMID 20505335.
- Séverine Landais, Sébastien Landry, Philippe Legault and al. (2007). "Oncogenic Potential of the miR-106-363 Cluster and Its Implication in Human T-Cell Leukemia". Cancer Res. 67 (12): 5699–707. PMID 17575136. doi:10.1158/0008-5472.CAN-06-4478.
- Johannes Grillari, Matthias Hackl, Regina Grillari-Voglauer (2010). "miR-17–92 cluster: ups and downs in cancer and aging". Biogerontology. 11: 501–506. PMC . PMID 20437201. doi:10.1007/s10522-010-9272-9.
- Virginie Olive, Margaux J. Bennett, James C. Walker and al. (2009). "miR-19 is a key oncogenic component of mir-17-92". Genes Dev. 23 (24): 2839–49. PMC . PMID 20008935. doi:10.1101/gad.1861409.
- Flavia Pichiorri, Sung-Suk Suh, Marco Ladetto and al. (2008). "MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis". 105 (35): 12885–90. PMC . PMID 18728182. doi:10.1073/pnas.0806202105.
- V Glorian, G Maillot, S Polès and al. (2011). "HuR-dependent loading of miRNA RISC to the mRNA encoding the Ras-related small GTPase RhoB controls its translation during UV-induced apoptosis". Cell Death and Differentiation. 18: 1692–1701. PMC . PMID 21527938. doi:10.1038/cdd.2011.35.
- Karina Conkrite, Maggie Sundby, Shizuo Mukai and al. (2011). "miR-17~92 cooperates with RB pathway mutations to promote retinoblastoma". 25 (16): 1734–45. PMC . PMID 21816922. doi:10.1101/gad.17027411.
- Joshua T. Mendell (2008). "miRiad roles for the miR-17-92 cluster in development and disease". 133 (2): 217–22. PMC . PMID 18423194. doi:10.1016/j.cell.2008.04.001.
- Karine Tréguer, Eva-Marie Heinrich, Kisho Ohtani and al. (2012). "Role of the MicroRNA-17–92 Cluster in the Endothelial Differentiation of Stem Cells". 49: 447–460. PMID 22797777. doi:10.1159/000339429.
- Andrea Ventura, Amanda G. Young, Monte M. Winslow and al. (2008). "Targeted deletion reveals essential and overlapping functions of the miR-17~92 family of miRNA clustersMechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3β". Cell. 132 (5): 875–886. PMC . PMID 18329372. doi:10.1016/j.cell.2008.02.019. Unknown parameter
- Lixin Hong, Maoyi Lai, Michelle Chen and al. (2010). "The miR-17-92 Cluster of microRNAs Confers Tumorigenicity by Inhibiting Oncogene-Induced Senescence". Cancer Res. 70 (21): 8547–8557. PMC . PMID 20851997. doi:10.1016/j.cell.2008.02.019. Unknown parameter
- JR-Shiuan Yang, Michael D. Phillips, Doron Betel and al. (2011). "Widespread regulatory activity of vertebrate microRNA* species". RNA. 17 (2): 312–26. PMC . PMID 21177881. doi:10.1016/j.cell.2008.02.019. Unknown parameter
- Joost Kluiver, Johan H. Gibcus, Chris Hettinga and al. (2012). "Rapid Generation of MicroRNA Sponges for MicroRNA Inhibition". PLoS One. 7 (1): e29275. PMC . PMID 22238599. doi:10.1371/journal.pone.0029275.
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