Mir-34 microRNA precursor family

Last updated
mir-34 microRNA precursor family
MicroRNA-34 precursor structure.svg
Predicted secondary structure and sequence conservation of mir-34
Identifiers
Symbolmir-34
Rfam RF00456
miRBase MI0000268
miRBase family MIPF0000039
Other data
RNA type Gene; miRNA
Domain(s) Eukaryota
GO GO:0035195 GO:0035068
SO SO:0001244
PDB structures PDBe

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 [1] and later verified experimentally. [2] [3] 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. [4]

Contents

The miR-34 family

In mammals, three miR-34 precursors are produced from two transcriptional units. [5] The human miR-34a precursor is transcribed from chromosome 1. The miR-34b and miR-34c precursors are co-transcribed from a region on chromosome 11, apparently as part of a transcript known as BC021736.

Expression of MIR34A (gene) in mouse is observed in all tissues examined but is highest in brain. miR-34b and -c are relatively less abundant in most tissues, but are the predominant miR-34 species in lung. [5] The presence of miR-34 products has also been confirmed in embryonic stem cells. miR-34 has been shown to be maternally inherited in Drosophila and zebrafish and the loss of miR-34 resulted in defects in hindbrain development in zebrafish embryos. This was the first report of knockdown phenotype of miR-34 in any model organism although the phenotype was observed in only about 30% of zebrafish embryos. [6]

Targets of miR-34

Yamakuchi et al.. showed that miR-34a targets the silent information regulator 1 (SIRT1) gene: [7]

"miR-34 inhibition of SIRT1 leads to an increase in acetylated p53 and expression of p21 and PUMA, transcriptional targets of p53 that regulate the cell cycle and apoptosis, respectively. Furthermore, miR-34 suppression of SIRT1 ultimately leads to apoptosis in WT human colon cancer cells but not in human colon cancer cells lacking p53. Finally, miR-34a itself is a transcriptional target of p53, suggesting a positive feedback loop between p53 and miR-34a. Thus, miR-34a functions as a tumor suppressor, in part, through a SIRT1-p53 pathway." [7]

Recently Quantitative proteomics – SILAC approach was used to identify miR-34a targets at genome level in HEK293T cells. [8]

Mir-34 inhibits human p53-mutant gastric cancer tumorspheres

p53-deficient human gastric cancer cells, restoration of functional miR-34 inhibits cell growth and induces chemosensitization and apoptosis, indicating that miR-34 may restore p53 function. Restoration of miR-34 inhibits tumorsphere formation and growth, which is reported to be correlated to the self-renewal of cancer stem cells. The mechanism of miR-34-mediated suppression of self-renewal appears to be related to the direct modulation of downstream targets Bcl-2, Notch, and HMGA2, indicating that miR-34 may be involved in gastric cancer stem cell self-renewal/differentiation decision-making. [9] [10] miR-34c has also been associated to bone development and bone cancer. [11]

Related Research Articles

mir-192/215 microRNA precursor

The miR-192 microRNA precursor, is a short non-coding RNA gene involved in gene regulation. miR-192 and miR-215 have now been predicted or experimentally confirmed in mouse and human.

mir-10 microRNA precursor family Short non-coding RNA gene

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-124 microRNA precursor family

The miR-124 microRNA precursor is a small non-coding RNA molecule that has been identified in flies, nematode worms, mouse and human. The mature ~21 nucleotide microRNAs are processed from hairpin precursor sequences by the Dicer enzyme, and in this case originates from the 3' arm. miR-124 has been found to be the most abundant microRNA expressed in neuronal cells. Experiments to alter expression of miR-124 in neural cells did not appear to affect differentiation. However these results are controversial since other reports have described a role for miR-124 during neuronal differentiation.

mir-129 microRNA precursor family

The miR-129 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. This microRNA was first experimentally characterised in mouse and homologues have since been discovered in several other species, such as humans, rats and zebrafish. The mature sequence is excised by the Dicer enzyme from the 5' arm of the hairpin. It was elucidated by Calin et al. that miR-129-1 is located in a fragile site region of the human genome near a specific site, FRA7H in chromosome 7q32, which is a site commonly deleted in many cancers. miR-129-2 is located in 11p11.2.

mir-15 microRNA precursor family

The miR-15 microRNA precursor family is made up of small non-coding RNA genes that regulate gene expression. The family includes the related mir-15a and mir-15b sequences, as well as miR-16-1, miR-16-2, miR-195 and miR-497. These six highly conserved miRNAs are clustered on three separate chromosomes. In humans miR-15a and miR-16 are clustered within 0.5 kilobases at chromosome position 13q14. This region has been found to be the most commonly affected in chronic lymphocytic leukaemia (CLL), with deletions of the entire region in more than half of cases. Both miR-15a and miR-16 are thus frequently deleted or down-regulated in CLL samples with 13q14 deletions; occurring in more than two thirds of CLL cases. The expression of miR-15a is associated with survival in triple negative breast cancer.

mir-199 microRNA precursor

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. 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.

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-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.

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-137

In molecular biology, miR-137 is a short non-coding RNA molecule that functions to regulate the expression levels of other genes by various mechanisms. miR-137 is located on human chromosome 1p22 and has been implicated to act as a tumor suppressor in several cancer types including colorectal cancer, squamous cell carcinoma and melanoma via cell cycle control.

mir-145 Non-coding RNA in the species Homo sapiens

In molecular biology, mir-145 microRNA is a short RNA molecule that in humans is encoded by the MIR145 gene. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

mir-184 Non-coding microRNA molecule

In molecular biology, miR-184 microRNA is a short non-coding RNA molecule. MicroRNAs (miRNAs) function as posttranscriptional regulators of expression levels of other genes by several mechanisms. Several targets for miR-184 have been described, including that of mediators of neurological development, apoptosis and it has been suggested that miR-184 plays an essential role in development.

miR-203

In molecular biology miR-203 is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms, such as translational repression and Argonaute-catalyzed messenger RNA cleavage. miR-203 has been identified as a skin-specific microRNA, and it forms an expression gradient that defines the boundary between proliferative epidermal basal progenitors and terminally differentiating suprabasal cells. It has also been found upregulated in psoriasis and differentially expressed in some types of cancer.

mir-31

miR-31 has been characterised as a tumour suppressor miRNA, with its levels varying in breast cancer cells according to the metastatic state of the tumour. From its typical abundance in healthy tissue is a moderate decrease in non-metastatic breast cancer cell lines, and levels are almost completely absent in mouse and human metastatic breast cancer cell lines. Mir-31-5p has also been observed upregulated in Zinc Deficient rats compared to normal in ESCC and in other types of cancers when using this animal model. There has also been observed a strong encapsulation of tumour cells expressing miR-31, as well as a reduced cell survival rate. miR-31's antimetastatic effects therefore make it a potential therapeutic target for breast cancer. However, these two papers were formally retracted by the authors in 2015.

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.

In molecular biology, microRNAs function to regulate the expression levels of other genes by several mechanisms. The miR-449 microRNA family encompasses three homologous small RNA molecules (miR-449a/b/c). This miR-449 cluster is located in the second intron of the CDC20B gene which both are co-transcribed. This miR-449 family belongs to the miR-34/miR-449 superfamily of microRNAs that is composed of six homologous miRNAs, named miR-34a/b/c and miR-449a/b/c.They are grouped together in the same superfamily, as their seed region and their adjacent nucleotide sequences are largely conserved. The miR-449 miRNAs control the differentiation of multiciliated cells in vertebrates.

<span class="mw-page-title-main">MIR34A</span> Non-coding RNA in the species Homo sapiens

MicroRNA 34a (miR-34a) is a MicroRNA that in humans is encoded by the MIR34A gene.

mIR141

MicroRNA 141 is a non-coding RNA molecule that in humans is encoded by the MIR141 gene.

<span class="mw-page-title-main">MicroRNA 93</span> Non-coding RNA in the species Homo sapiens

MicroRNA 93 is a functional RNA and a microRNA that in humans is encoded by the MIR93 gene.

References

  1. ↑ Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP (Mar 2003). "Vertebrate microRNA genes". Science. 299 (5612): 1540. doi:10.1126/science.1080372. PMID   12624257. S2CID   37750545.
  2. ↑ Dostie J, Mourelatos Z, Yang M, Sharma A, Dreyfuss G (Feb 2003). "Numerous microRNPs in neuronal cells containing novel microRNAs". RNA. 9 (2): 180–6. doi:10.1261/rna.2141503. PMC   1370383 . PMID   12554860.
  3. ↑ Houbaviy HB, Murray MF, Sharp PA (Aug 2003). "Embryonic stem cell-specific MicroRNAs". Developmental Cell. 5 (2): 351–8. doi: 10.1016/S1534-5807(03)00227-2 . PMID   12919684.
  4. ↑ He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, Jackson AL, Linsley PS, Chen C, Lowe SW, Cleary MA, Hannon GJ (Jun 2007). "A microRNA component of the p53 tumour suppressor network". Nature. 447 (7148): 1130–4. doi:10.1038/nature05939. PMC   4590999 . PMID   17554337.
  5. 1 2 Hermeking H (Feb 2010). "The miR-34 family in cancer and apoptosis". Cell Death and Differentiation. 17 (2): 193–9. doi:10.1038/cdd.2009.56. PMID   19461653. S2CID   25936686.
  6. ↑ Soni K, Choudhary A, Patowary A, Singh AR, Bhatia S, Sivasubbu S, Chandrasekaran S, Pillai B (Apr 2013). "miR-34 is maternally inherited in Drosophila melanogaster and Danio rerio". Nucleic Acids Research. 41 (8): 4470–80. doi:10.1093/nar/gkt139. PMC   3632126 . PMID   23470996.
  7. 1 2 Yamakuchi M, Ferlito M, Lowenstein CJ (Sep 2008). "miR-34a repression of SIRT1 regulates apoptosis". Proceedings of the National Academy of Sciences of the United States of America. 105 (36): 13421–6. doi: 10.1073/pnas.0801613105 . PMC   2533205 . PMID   18755897.
  8. ↑ Bargaje R, Gupta S, Sarkeshik A, Park R, Xu T, Sarkar M, Halimani M, Roy SS, Yates J, Pillai B (2012). "Identification of novel targets for miR-29a using miRNA proteomics". PLOS ONE. 7 (8): e43243. doi: 10.1371/journal.pone.0043243 . PMC   3428309 . PMID   22952654.
  9. ↑ Ji Q, Hao X, Meng Y, Zhang M, Desano J, Fan D, et al. (2008). "Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres". BMC Cancer. 8: 266. doi: 10.1186/1471-2407-8-266 . PMC   2564978 . PMID   18803879.
  10. ↑ Mir-34 and p53 pathway
  11. ↑ Bae Y, Yang T, Zeng HC, Campeau PM, Chen Y, Bertin T, Dawson BC, Munivez E, Tao J, Lee BH (Jul 2012). "miRNA-34c regulates Notch signaling during bone development". Human Molecular Genetics. 21 (13): 2991–3000. doi:10.1093/hmg/dds129. PMC   3373245 . PMID   22498974.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.