Mir-1 microRNA precursor family

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miR-1
RF00103.jpg
mIR-1 microRNA precursor family
Identifiers
Symbolmir-1
Rfam RF00103
miRBase MI0000651
miRBase family MIPF0000038
NCBI Gene 406904
HGNC HGNC:31499
OMIM 609326
Other data
RNA typeGene; miRNA;
Domain(s) Metazoa
GO 0035195
SO 0001244
Locus Chr. 20 q13.33
PDB structures PDBe

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. [1] 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.

Contents

These micro RNAs have pivotal roles in development and physiology of muscle tissues including the heart. [2] [3] MiR-1 is known to play an important role in heart diseases such as hypertrophy, myocardial infarction, and arrhythmias. [4] [5] [6] Studies have shown that MiR-1 is an important regulator of heart adaption after ischemia or ischaemic stress and it is upregulated in the remote myocardium of patients with myocardial infarction. [7] Also MiR-1 is downregulated in myocardial infarcted tissue compared to healthy heart tissue. [8] Plasma levels of MiR-1 can be used as a sensitive biomarker for myocardial infarction. [9]

Targets of miR-1

The heat shock protein, HSP60 is also known to be a target for post-transcriptional regulation by miR-1 and miR-206. HSP60 is a component of the defence mechanism against diabetic myocardial injury and its level is reduced in the diabetic myocardium. In both in vivo and in vitro experiments increased levels of glucose in myocardiomyctes led to significant upregulation of miR-1 and miR-206 with resulting modulation of HSP60 leading to accelerated glucose-mediated apoptosis in cardiomyocytes. [10]

MiR-1 has key roles in the development and differentiation of smooth and skeletal muscles. [11] [12] [13] For example, in the lineage-specific differentiation of smooth muscle cells from embryonic stem cell derived cultures, MiR-1 is required; as its loss of function resulted in a reduction in smooth muscle cell biomarkers and a reduction in the derived smooth muscle cell population. There is evidence that the control of smooth muscle cell differentiation by MiR-1 may be mediated by the down regulation of Kruppel-like factor 4 (KLF4), since a MiR-1 recognition site is predicted in the 3' UTR of KLF4 and inhibition of MiR-1 results in reversed down-regulation of KLF4 and an inhibition of smooth muscle cell differentiation. [14] A mutation in the 3' UTR of the myostatin gene in Texel sheep creates a miR-1 and miR-206 target site. This is likely to cause the muscular phenotype of this breed of sheep. [15]

Clinical relevance of miR-1

Mir-1 plays an important role in some cancers. Rhabdomyosarcoma is the most common soft tissue sarcoma in children. Since the tumor results from undifferentiated cells, agents that promote differentiation hold promise as possible therapies. A study showed that levels of mir-1 and mir-133a were drastically reduced in tumourous cell lines whilst their targets were up-regulated. [16]

Introduction of miR-1 and miR-133a into an embryonal rhabdomyosarcoma-derived cell line is cytostatic, which suggested a strong tumour-suppressive role for these microRNAs. Expression of miR-1 but not miR-133a gave transcriptional profiles that were consistent with a strong promyogenic influence on the cells, again demonstrating the role of miR-1 in muscle differentiation from precursor stem cells. The authors propose that miR-1 and miR-133a act to repress isoforms of genes that are not normally expressed in muscle cells. All of these observations suggest that mis-regulation of miR-1 and miR-133a can result in tumorogenesis via abolition of the suppressive effect they have on certain gene targets and of the removal of the promotion of differentiation of the cells exerted my miR-1. [16]

The involvement of miR-1 in cancer is not limited to cancers of muscle and muscle tissues. MiR-1 may have a tumour-suppressive effect in bladder cancer by regulation of LIM and SH3 protein 1 (LASP1) . [17]

There is evidence for the role of miR-1-2 as a modulator in acute myeloid leukemia via its transcription by the zinc-finger transcription factor, EVI1, ectopic virus expression site 1. ChIP assays have shown that EVI1 binds strongly to the promoters of miR-1-2 and miR-133-a-1, and expression of EVI1 is significantly correlated with the expression of miR-1-2 and miR-133-a-1 in established cell lines and in patient samples. However, only miR-1-2 was involved in abnormal proliferation in EVI1 expressing cell lines. [18]

miR-1 and related microRNA miR-499 are proposed to be involved in the regulation of hepatocellular carcinoma (HCC) pathogenesis. [19] These two microRNAs have been shown to downregulate the expression of the ets1 proto-oncogene in cell lines HepG2 by targeting the 3'UTR of ets1. ets1 is involved in extracellular matrix (ECM) degradation which is an important process required for tumor cell invasion and migration.

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 silence said mRNA molecules by one or more of the following processes:

  1. Cleavage of the mRNA strand into two pieces,
  2. Destabilization of the mRNA by shortening its poly(A) tail, or
  3. Reducing translation of the 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-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-133 microRNA precursor family

mir-133 is a type of non-coding RNA called a microRNA that was first experimentally characterised in mice. Homologues have since been discovered in several other species including invertebrates such as the fruitfly Drosophila melanogaster. Each species often encodes multiple microRNAs with identical or similar mature sequence. For example, in the human genome there are three known miR-133 genes: miR-133a-1, miR-133a-2 and miR-133b found on chromosomes 18, 20 and 6 respectively. The mature sequence is excised from the 3' arm of the hairpin. miR-133 is expressed in muscle tissue and appears to repress the expression of non-muscle genes.

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-24 microRNA precursor family

The miR-24 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a mature ~22 nucleotide product. 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. miR-24 is conserved in various species, and is clustered with miR-23 and miR-27, on human chromosome 9 and 19. Recently, miR-24 has been shown to suppress expression of two crucial cell cycle control genes, E2F2 and Myc in hematopoietic differentiation and also to promote keratinocyte differentiation by repressing actin-cytoskeleton regulators PAK4, Tsk5 and ArhGAP19.

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-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-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-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-451 microRNA

In molecular biology mir-451 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

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-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.

In molecular biology mir-370 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. This microRNA, mir-370-3p, has been shown to play a role in heart failure. The upregulation of mir-370-3p in the sinus node leads to downregulation of the pacemaker ion channel, HCN4, and thus downregulation of the corresponding ionic current, which causes sinus bradycardia.

miR-324-5p is a microRNA that functions in cell growth, apoptosis, cancer, epilepsy, neuronal differentiation, psychiatric conditions, cardiac disease pathology, and more. As a microRNA, it regulates gene expression through targeting mRNAs. Additionally, miR-324-5p is both an intracellular miRNA, meaning it is commonly found within the microenvironment of the cell, and one of several circulating miRNAs found throughout the body. Its presence throughout the body both within and external to cells may contribute to miR-324-5p's wide array of functions and role in numerous disease pathologies – especially cancer – in various organ systems.

References

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Further reading