Mir-8/mir-141/mir-200 microRNA precursor family

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mir-8/mir-141/mir-200 microRNA precursor family
RF00241.jpg
Predicted secondary structure and sequence conservation of mir-8
Identifiers
Symbolmir-8
Rfam RF00241
miRBase MI0000128
miRBase family MIPF0000019
Other data
RNA type Gene; miRNA
Domain(s) Eukaryota
GO GO:0035195 GO:0035068
SO SO:0001244
PDB structures PDBe

The miR-8 microRNA precursor (homologous to miR-141, miR-200, miR-236), is a short non-coding RNA gene involved in gene regulation. miR-8 in Drosophila melanogaster [1] is expressed from the 3' arm of related precursor hairpins (represented here), along with miR-200, [2] miR-236, [1] miR-429 and human and mouse homolog miR-141. Members of this precursor family have now been predicted or experimentally confirmed in a wide range of species. The bounds of the precursors are predicted based on conservation and base pairing and are not generally known.

Contents

The miR-200 family is highly conserved in bilaterian animals, with miR-8 as the sole homolog in Drosophila. This species has accordingly been used heavily in work looking to uncover the biological function of the miR-200 family. [3] miR-8 has been observed at all developmental stages of the embryo, and is present in cultured S2 cells of D. melanogaster. [1] Its expression has been seen to be strongly upregulated in larvae and this expression then sustained through to adulthood.

Targets of miR-8

The atrophin gene has been shown to be a target of Drosophila miR-8., [4] with suggestion that this target is also conserved in mammalian miR-8. Elevated atrophin activity in miR-8 mutant phenotypes has been observed, this in turn inducing elevated neural apoptosis and also behavioural defects. The atrophin mRNA increase in miR-8 mutants occurs post-transcriptionally, with miR-8 binding leading to destabilisation of atrophin mRNA. miR-8 acts to control atrophin expression in vivo directly via miR-8 sites in its 3'UTR. Indeed, a statistically significant increase in surviving adults following the removal of one copy of the atrophin gene has shown atrophin mRNA to be a functionally important target in vivo. This supports the theory that a misregulation of atrophin contributes to the defects seen in miR-8 mutants. Atrophin protein levels have additionally been found to be detectably higher in miR-8 mutant brains. [4] The neural effects of miR-8 in miR-8-expressing cells are likely to be concentrated in miR-8-expressing neurons, therefore only acting to affect certain neuron functions.

A tuning target relationship is in place between atrophin levels and miR-8 regulation. [4] The level of atrophin below that reached by miR-8 regulation is detrimental for the continued functioning of miR-8-expressing cells. The atrophin level here is required at an optimal level to ensure the avoidance of developmental defects arising due to decreased atrophin expression.

The human miR-200c is likely to target the Zinc Finger Transcription Factor 8 (TCF8) gene. [5]

Regulation of insulin signalling

miR-8, together with miR-200, has been identified as a regulator of insulin signalling in Drosophila fat body, the equivalent of liver and adipose tissue combined. [3] This has led to speculation about further roles of these two members of this miRNA precursor family. mir-8 regulates body size in Drosophila in conjunction with its target USH, and the homolog miR-200 works in the same way with its respective target FOG2. Phosphoinositide 3-kinase (PI3K) is a kinase involved in a phosphorylation cascade which, once activated, works to enhance cell growth and proliferation. USH and FOG2 are able to inhibit PI3K activity through direct interaction with its regulatory subunits, dp60 and p85α respectively. This prevents the formation of an active PI3K complex. Elevated USH/F0G2 levels are observed in miR-8/200 null larvae, with a resultant downregulation in the PI3K activity of these larvae. In the presence of miR-8/200, insulin signalling in the fat body region is enhanced, and further cell size increases are seen with miR-8/200 overexpression. [3] The effect of miR-8/200 on cell growth through insulin signalling has been found to vary in differing tissue types.

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-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-130 microRNA precursor family

In molecular biology, miR-130 microRNA precursor is a small non-coding RNA that regulates gene expression. This microRNA has been identified in mouse, and in human. miR-130 appears to be vertebrate-specific miRNA and has now been predicted or experimentally confirmed in a range of vertebrate species. Mature microRNAs are processed from the precursor stem-loop by the Dicer enzyme. In this case, the mature sequence is excised from the 3' arm of the hairpin. It has been found that miR-130 is upregulated in a type of cancer called hepatocellular carcinoma. It has been shown that miR-130a is expressed in the hematopoietic stem/progenitor cell compartment but not in mature blood cells.

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-194 microRNA precursor family

In molecular biology, miR-194 microRNA precursor is a small non-coding RNA gene that regulated gene expression. Its expression has been verified in mouse and in human. mir-194 appears to be a vertebrate-specific miRNA and has now been predicted or experimentally confirmed in a range of vertebrate species. The mature microRNA is processed from the longer hairpin precursor by the Dicer enzyme. In this case, the mature sequence is excised from the 5' arm of the hairpin.

mir-219 microRNA precursor family

In molecular biology, the microRNA miR-219 was predicted in vertebrates by conservation between human, mouse and pufferfish and cloned in pufferfish. It was later predicted and confirmed experimentally in Drosophila. Homologs of miR-219 have since been predicted or experimentally confirmed in a wide range of species, including the platyhelminth Schmidtea mediterranea, several arthropod species and a wide range of vertebrates. The hairpin precursors are predicted based on base pairing and cross-species conservation; their extents are not known. In this case, the mature sequence is excised from the 5' arm of the hairpin.

mir-2 microRNA precursor

The mir-2 microRNA family includes the microRNA genes mir-2 and mir-13. Mir-2 is widespread in invertebrates, and it is the largest family of microRNAs in the model species Drosophila melanogaster. MicroRNAs from this family are produced from the 3' arm of the precursor hairpin. Leaman et al. showed that the miR-2 family regulates cell survival by translational repression of proapoptotic factors. Based on computational prediction of targets, a role in neural development and maintenance has been suggested.

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-6 microRNA precursor

The mir-6 microRNA precursor is a precursor microRNA specific to Drosophila species. In Drosophila melanogaster there are three mir-6 paralogs called dme-mir-6-1, dme-mir-6-2, dme-mir-6-3, which are clustered together in the genome. The extents of these hairpin precursors are estimated based on hairpin prediction. Each precursor is generated following the cleavage of a longer primary transcript in the nucleus, and is exported in the cytoplasm. In the cytoplasm, precursors are further processed by the enzyme Dicer, generating ~22 nucleotide products from each arm of the hairpin. The products generated from the 3' arm of each mir-6 precursor have identical sequences. Both 5' and 3' mature products are experimentally validated. Experimental data suggests that the mature products of mir-6 hairpins are expressed in the early embryo of Drosophila and target apoptotic genes such as hid, grim and rpr.

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.

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-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-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.

In molecular biology mir-361 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. For example, miR-361-5p might act as a suppressor in triple-negative breast cancer (TNBC) by targeting RQCD1 to inhibit the EGFR/PI3K/Akt signaling pathway.

In molecular biology mir-14 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-278 microRNA is a short RNA molecule belonging to a class of molecules referred to as microRNAs. These function to regulate the expression levels of other genes by several mechanisms, primarily binding to their target at its 3'UTR.

mir-279 is a short RNA molecule found in Drosophila melanogaster that belongs to a class of molecules known as microRNAs. microRNAs are ~22nt-long non-coding RNAs that post-transcriptionally regulate the expression of genes, often by binding to the 3' untranslated region of mRNA, targeting the transcript for degradation. miR-279 has diverse tissue-specific functions in the fly, influencing developmental processes related to neurogenesis and oogenesis, as well as behavioral processes related to circadian rhythms. The varied roles of mir-279, both in the developing and adult fly, highlight the utility of microRNAs in regulating unique biological processes.

In molecular biology mir-872 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

References

  1. 1 2 3 Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001). "Identification of novel genes coding for small expressed RNAs". Science. 294 (5543): 853–8. doi:10.1126/science.1064921. hdl: 11858/00-001M-0000-0012-F65F-2 . PMID   11679670.
  2. ↑ Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T (2003). "New microRNAs from mouse and human". RNA. 9 (2): 175–9. doi:10.1261/rna.2146903. PMC   1370382 . PMID   12554859.
  3. 1 2 3 Hyun S, Lee JH, Jin H, Nam J, Namkoong B, Lee G, et al. (2009). "Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K". Cell. 139 (6): 1096–108. doi: 10.1016/j.cell.2009.11.020 . PMID   20005803.
  4. 1 2 3 Karres JS, Hilgers V, Carrera I, Treisman J, Cohen SM (2007). "The Conserved microRNA MiR-8 Tunes Atrophin Levels to Prevent Neurodegeneration in Drosophila". Cell. 131 (1): 136–45. doi: 10.1016/j.cell.2007.09.020 . PMID   17923093.
  5. ↑ Hurteau GJ, Carlson JA, Spivack SD, Brock GJ (2007). "Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin". Cancer Res. 67 (17): 7972–6. doi:10.1158/0008-5472.CAN-07-1058. PMID   17804704.
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