Mir-127

Last updated
mir-127
MiR-127 secondary structure.png
miR-127 microRNA secondary structure and sequence conservation
Identifiers
Symbolmir-127
Rfam RF00676
miRBase family MIPF0000080
NCBI Gene 406914
HGNC 31509
OMIM 611709
Other data
RNA type microRNA
Domain(s) Eukaryota;
PDB structures PDBe

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.

Contents

Gene structure

pri-miR-127 is derived from a separate but overlapping conserved gene cluster coding for miR-433/127. miR-127 and miR-433 are overlapped in a 5'-3' direction. [1] Although the loci could be found on different chromosomes in different species, the structure has been conserved. In mammals including human, chimpanzee, horse, dog, monkey, rat, cow, and mouse, multiple sequence alignments (MSA) between miR-433 and miR127 have shown 95-100% similarity with a conserved distance between miR-433 and miR-127 of 986 to 1007 bp. Moreover, the upstream response elements in the miR-433/127 promoters, including estrogen related receptors response element (ERRE) have been conserved among above species. Data have suggested that that miR-433/127 loci may have evolved from a common gene of origin. [2]

Transcription regulation

Transcription factor binding sites positioned upstream of miRNA precursor play a role in regulating transcription. Activation of miR-127 and miR-433 promoters is mediated by estrogen-related receptor gamma (ERRgamma, NR3B3), which physically associates with their endogenous promoters. Inhibition is regulated by Small heterodimer partner (SHP), which acts in trans. [3] Although miR-127 and miR-433 have common regulatory elements, they have independent promoters and their differential expression pattern is observed. [4]

Functional roles

Down-regulation of the imprinted gene Rtl1

Rtl1 is a key gene in placenta formation and the loss or overexpression of Rlt1 have led to late-fetal or neonatal lethality in mice. [5] miR-127 is located near CpG islands in the imprinted region encoding rtl1 and is normally transcribed in an antisense orientation to the gene. Ectopic expression of miR-127 resulted in a reduction in Rtl1 expression in Human Hela cell and mouse Heppa-1.

Experiments performed in mice showed that Rtl1 was only transcribed from the paternal chromosome, while the maternal allele was degraded. miR-127 and miR-136 however, are only maternally expressed in the somatic cells and thus play a role in antisense regulation of Rtl1 imprinting. Aberrant methylation status of Rtl1 and miR-127 indicated that epigenetic programming is also involved in the process. [2]

Control of fetal lung development

miR-127 is highly expressed in late state of fetal development. A disruption to the system by overexpressing miR-127 in a fetal lung organ culture system resulted in defective development shown by a decrease in terminal bud counts and varied bud sizes. [6]

Role in disease

Diffuse large B-cell lymphoma

Upregulation of miR-127 caused a downregulation of B-cell lymphoma 6 protein, a proto-oncogene which is usually hypermutated in diffuse large B-cell lymphoma (DLCL). [7] [8] Moreover, differential expression of miR-127 was detected in different type of DLCL. miR-127 levels were significantly higher in the testicular DLCL compared with the nodal and central nervous system DLCL, implying different biological entity of DLCL in different locations. [9]

Hepatocellular carcinoma

Inhibition of miR-127 expression is linked with Hepatocellular carcinoma. The mechanistic link was confirmed by a change in BCL6 protein, which is targeted by miR-127. [10]

See also

Related Research Articles

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-16 microRNA precursor family

The miR-16 microRNA precursor family is a group of related small non-coding RNA genes that regulates gene expression. miR-16, miR-15, mir-195 and miR-497 are related microRNA precursor sequences from the mir-15 gene family. This microRNA family appears to be vertebrate specific and its members have been predicted or experimentally validated in a wide range of vertebrate species.

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-29 microRNA precursor

The miR-29 microRNA precursor, or pre-miRNA, is a small RNA molecule in the shape of a stem-loop or hairpin. Each arm of the hairpin can be processed into one member of a closely related family of short non-coding RNAs that are involved in regulating gene expression. The processed, or "mature" products of the precursor molecule are known as microRNA (miRNA), and have been predicted or confirmed in a wide range of species.

mir-7 microRNA precursor

This family represents the microRNA (miRNA) precursor mir-7. This miRNA has been predicted or experimentally confirmed in a wide range of species. miRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. In this case the mature sequence comes from the 5' arm of the precursor. The extents of the hairpin precursors are not generally known and are estimated based on hairpin prediction. The involvement of Dicer in miRNA processing suggests a relationship with the phenomenon of RNA interference.

MTA1

Metastasis-associated protein MTA1 is a protein that in humans is encoded by the MTA1 gene. MTA1 is the founding member of the MTA family of genes. MTA1 is primarily localized in the nucleus but also found to be distributed in the extra-nuclear compartments. MTA1 is a component of several chromatin remodeling complexes including the nucleosome remodeling and deacetylation complex (NuRD). MTA1 regulates gene expression by functioning as a coregulator to integrate DNA-interacting factors to gene activity. MTA1 participates in physiological functions in the normal and cancer cells. MTA1 is one of the most upregulated proteins in human cancer and associates with cancer progression, aggressive phenotypes, and poor prognosis of cancer patients.

MTA3

Metastasis-associated protein MTA3 is a protein that in humans is encoded by the MTA3 gene. MTA3 protein localizes in the nucleus as well as in other cellular compartments MTA3 is a component of the nucleosome remodeling and deacetylate (NuRD) complex and participates in gene expression. The expression pattern of MTA3 is opposite to that of MTA1 and MTA2 during mammary gland tumorigenesis. However, MTA3 is also overexpressed in a variety of human cancers.

mir-143

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-433

In molecular biology, mir-433 is a short non-coding RNA molecule. MicroRNAs (miRNAs) function as posttranscriptional regulators of expression levels of other genes by several mechanisms. They play roles in development, metabolism and carcinogenesis.

mir-221 microRNA

In molecular biology, mir-221 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.

In molecular biology mir-365 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-497 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-153 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-190 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

mir-618 microRNA is a short non-coding RNA molecule belonging both to the family of microRNAs and to that of small interfering RNAs (siRNAs). MicroRNAs function to regulate the expression levels of other genes by several mechanisms, whilst siRNAs are involved primarily with the RNA interference (RNAi) pathway.

In molecular biology mir-765 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

References

  1. ↑ Song G, Wang L (2008). Volff, Jean-Nicolas (ed.). "MiR-433 and miR-127 arise from independent overlapping primary transcripts encoded by the miR-433-127 locus". PLOS ONE. 3 (10): e3574. doi: 10.1371/journal.pone.0003574 . PMC   2570487 . PMID   18974780.
  2. 1 2 Song G, Wang L (2009). Tora, Laszlo (ed.). "A conserved gene structure and expression regulation of miR-433 and miR-127 in mammals". PLOS ONE. 4 (11): e7829. doi: 10.1371/journal.pone.0007829 . PMC   2778354 . PMID   19946636.
  3. ↑ Wang L, Liu J, Saha P, et al. (October 2005). "The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes". Cell Metab. 2 (4): 227–38. doi: 10.1016/j.cmet.2005.08.010 . PMID   16213225.
  4. ↑ Song G, Wang L (October 2008). "Transcriptional mechanism for the paired miR-433 and miR-127 genes by nuclear receptors SHP and ERRgamma". Nucleic Acids Res. 36 (18): 5727–35. doi:10.1093/nar/gkn567. PMC   2566885 . PMID   18776219.
  5. ↑ Sekita Y, Wagatsuma H, Nakamura K, et al. (February 2008). "Role of retrotransposon-derived imprinted gene, Rtl1, in the feto-maternal interface of mouse placenta". Nat. Genet. 40 (2): 243–8. doi:10.1038/ng.2007.51. PMID   18176565. S2CID   5455176.
  6. ↑ Bhaskaran M, Wang Y, Zhang H, et al. (May 2009). "MicroRNA-127 modulates fetal lung development". Physiol. Genomics. 37 (3): 268–78. doi:10.1152/physiolgenomics.90268.2008. PMC   2685501 . PMID   19439715.
  7. ↑ Lu J, Getz G, Miska EA, et al. (June 2005). "MicroRNA expression profiles classify human cancers". Nature. 435 (7043): 834–8. doi:10.1038/nature03702. PMID   15944708. S2CID   4423938.
  8. ↑ Saito Y, Liang G, Egger G, et al. (June 2006). "Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells". Cancer Cell. 9 (6): 435–43. doi: 10.1016/j.ccr.2006.04.020 . PMID   16766263.
  9. ↑ Robertus JL, Harms G, Blokzijl T, et al. (April 2009). "Specific expression of miR-17-5p and miR-127 in testicular and central nervous system diffuse large B-cell lymphoma". Mod. Pathol. 22 (4): 547–55. doi: 10.1038/modpathol.2009.10 . PMID   19287466.
  10. ↑ Tryndyak VP, Ross SA, Beland FA, Pogribny IP (June 2009). "Down-regulation of the microRNAs miR-34a, miR-127, and miR-200b in rat liver during hepatocarcinogenesis induced by a methyl-deficient diet". Mol. Carcinog. 48 (6): 479–87. doi:10.1002/mc.20484. PMID   18942116. S2CID   25308355.

Further reading

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.