Mir-2 microRNA precursor

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mir-2 microRNA precursor
RF00047.jpg
Predicted secondary structure and sequence conservation of mir-2
Identifiers
Symbolmir-2
Rfam RF00047
miRBase MI0000117
miRBase family MIPF0000049
Other data
RNA type Gene; miRNA
Domain(s) Eukaryota
GO GO:0035195 GO:0035068
SO SO:0001244
PDB structures PDBe

The mir-2 microRNA family includes the microRNA genes mir-2 and mir-13 (MIPF0000049). 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. [1] Leaman et al. showed that the miR-2 family regulates cell survival by translational repression of proapoptotic factors. [2] Based on computational prediction of targets, a role in neural development and maintenance has been suggested. [1]

Contents

Species distribution

The mir-2 family is specific to protostomes. [1] There are 8 mir-2-related loci in Drosophila melanogaster : mir-2a-1, mir-2a-2, mir-2b-1, mir-2b-2, mir-2c, mir-13a, mir-13b-1 and mir-13b-2. [3] Most other insect genomes host five mir-2 loci [4] although the number varies in other invertebrates. [1] Mir-13 subfamily emerged from mir-2 sequences before the insect radiation. [1]

Although mir-11 and mir-6 have similar sequences to mir-2 microRNAs, they are not evolutionarily related, [1] and therefore should not be considered from the same microRNA family.

Consensus structure of the mir-2 family hairpin precursor. Mir-2 precursor.png
Consensus structure of the mir-2 family hairpin precursor.

Mir-2 hairpin precursor sequences are highly conserved, in particular in their 3' arm in which the first 10 nucleotides are identical to all family members. Functional mir-2 microRNAs come from the 3' arm of the precursors, and most of them have the same Drosha processing point. [1] [3] [5] That means that the seed sequence is virtually the same in all these products, [6] hence, they should target the same transcripts.

Genomic distribution of mir-2 microRNAs in fruitfly and red flour beetle genomes. Mir2 genomic structures.png
Genomic distribution of mir-2 microRNAs in fruitfly and red flour beetle genomes.

Mir-2 microRNAs are organized in a large cluster in most insects. This cluster has typically 5 members of the mir-2 family plus mir-71, an evolutionarily unrelated microRNA. [1] [4] The number of mir-2 sequences differs among invertebrate lineages although they remain tightly clustered in the genome. A notable exception has been observed in Drosophila melanogaster , in which the mir-2 family is organized in two clusters and two single loci. [3] Additionally, mir-7 microRNA has been lost in the Drosophila lineage. [4]

Origin and evolution

The mir-2 family originated before the last common ancestor of protostomes, and has been ever since linked to mir-71. [1] The evolution of mir-2 is characterized by successive expansions by duplication events. Since most paralogous microRNAs conserve their function, it has been suggested that mir-2 evolution is dominated by a birth-and-death dynamics driven by random drift. [1]

One mir-2 microRNA in Drosophila, dme-miR-2a-2 , is two nucleotides offset with respect to the canonical products of other mir-2 precursors. [5] This is likely to affect the function of that particular microRNA. This functional shift is associated to a change in the genomic distribution of mir-2 sequences in Drosophila. The functional diversification of microRNAs may require breaking the genomic linkage between paralogs, probably to avoid the co-regulation of multiple products by the same regulatory sequences. [1]

In the human parasite Schistosoma mansoni the whole mir-71/mir-2 cluster has been duplicated, and one of the copies is in the sexual chromosome. [7]

Targets of mir-2/mir-13

Mir-2 microRNAs in Drosophila specifically target three pro-apoptotic genes: rpr, grim and skl. [2] The repression of rpr and grim by the Hox gene ABD-B prevents apoptosis in neural cells. [8] On the other hand, computational prediction of microRNA targets show that mir-2 may target neural genes in both Drosophila and Caenorhabditis elegans . [1] All this suggests a conserved role of mir-2 in neural development and maintenance. [1] However, further experiments are required to confirm this association.

See also

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mir-46/mir-47/mir-281 microRNA precursor family

In molecular biology, mir-46 and mir-47 are microRNA expressed in C. elegans from related hairpin precursor sequences. The predicted hairpin precursor sequences for Drosophila mir-281 are also related and, hence, belong to this family. The hairpin precursors are predicted based on base pairing and cross-species conservation; their extents are not known. In this case, the mature sequences are expressed from the 3' arms of the hairpin precursors.

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

The miR-8 microRNA precursor, is a short non-coding RNA gene involved in gene regulation. miR-8 in Drosophila melanogaster is expressed from the 3' arm of related precursor hairpins, along with miR-200, miR-236, 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.

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-196 microRNA precursor family

miR-196 is a non-coding RNA called a microRNA that has been shown to be expressed in humans and mice. miR-196 appears to be a vertebrate specific microRNA and has now been predicted or experimentally confirmed in a wide range of vertebrate species. In many species the miRNA appears to be expressed from intergenic regions in HOX gene clusters. 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-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:

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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-96 microRNA

miR-96 microRNA precursor is a small non-coding RNA that regulates gene expression. microRNAs are transcribed as ~80 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~23 nucleotide products. In this case the mature sequence comes from the 5′ arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA.

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References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 Marco A, Hooks K, Griffiths-Jones S (March 2012). "Evolution and function of the extended miR-2 microRNA family". RNA Biology. 9 (3): 242–8. doi:10.4161/rna.19160. PMC   3384581 . PMID   22336713.
  2. 1 2 Leaman D, Chen PY, Fak J, Yalcin A, Pearce M, Unnerstall U, Marks DS, Sander C, Tuschl T, Gaul U (July 2005). "Antisense-mediated depletion reveals essential and specific functions of microRNAs in Drosophila development". Cell. 121 (7): 1097–108. doi:10.1016/j.cell.2005.04.016. hdl: 11858/00-001M-0000-0012-EB54-F . PMID   15989958. S2CID   2463749.
  3. 1 2 3 Ruby JG, Stark A, Johnston WK, Kellis M, Bartel DP, Lai EC (December 2007). "Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs". Genome Research. 17 (12): 1850–64. doi:10.1101/gr.6597907. PMC   2099593 . PMID   17989254.
  4. 1 2 3 Marco A, Hui JH, Ronshaugen M, Griffiths-Jones S (2010). "Functional shifts in insect microRNA evolution". Genome Biology and Evolution. 2: 686–96. doi:10.1093/gbe/evq053. PMC   2956262 . PMID   20817720.
  5. 1 2 Wang X, Liu XS (2011). "Systematic Curation of miRBase Annotation Using Integrated Small RNA High-Throughput Sequencing Data for C. elegans and Drosophila". Frontiers in Genetics. 2: 25. doi: 10.3389/fgene.2011.00025 . PMC   3268580 . PMID   22303321.
  6. ↑ Bartel DP (January 2009). "MicroRNAs: target recognition and regulatory functions". Cell. 136 (2): 215–33. doi:10.1016/j.cell.2009.01.002. PMC   3794896 . PMID   19167326.
  7. ↑ de Souza Gomes M, Muniyappa MK, Carvalho SG, Guerra-Sá R, Spillane C (August 2011). "Genome-wide identification of novel microRNAs and their target genes in the human parasite Schistosoma mansoni". Genomics. 98 (2): 96–111. doi: 10.1016/j.ygeno.2011.05.007 . PMID   21640815.
  8. ↑ Miguel-Aliaga I, Thor S (December 2004). "Segment-specific prevention of pioneer neuron apoptosis by cell-autonomous, postmitotic Hox gene activity". Development. 131 (24): 6093–105. doi:10.1242/dev.01521. PMID   15537690.
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