Mir-29 microRNA precursor

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mir-29 microRNA precursor
RF00074.jpg
Predicted secondary structure and sequence conservation of mir-29
Identifiers
Symbolmir-29
Rfam RF00074
miRBase MI0000087
miRBase family MIPF0000009
Other data
RNA type Gene; miRNA
Domain(s) Eukaryota
GO GO:0035195 GO:0035068
SO SO:0001244
PDB structures PDBe

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. [1] 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 (see 'MIPF0000009' in miRBase: the microRNA database).

Contents

miRNA processing

Animal miRNAs are first transcribed as a primary miRNA molecule. This "pri-miRNA" may contain one or more precursor hairpins, which are freed from the pri-miRNA by the nuclear enzyme Drosha. The approximately 70 nucleotide precursor hairpin is exported from the nucleus and subsequently processed by the Dicer enzyme to give a mature miRNA that is on average 22 nucleotides long. Either arm of the precursor may yield a mature RNA, although either the 3' (3p) or the 5' (5p) arm is preferentially processed and loaded into the RNA-induced silencing complex (RISC) in most cases. For the miR-29 precursor, the 3' arm of the precursor RNA yields the overwhelmingly predominant product (miR-29 or miR-29-3p), although the 5' arm (miR-29* or miR-29-5p) has also been experimentally verified.

The miR-29 family

Many mammalian genomes encode four closely related miR-29 precursors that are transcribed in two transcriptional units. For example, human miR-29a and miR-29b-1 are processed from an intron of a long non-coding transcript (LOC646329) from chromosome 7. miR-29b-2 (identical in sequence to miR-29b-1) and miR-29c are co-transcribed from chromosome 1. The three main mature miRNAs processed from these precursors are known as hsa-miR-29a, hsa-miR-29b, and hsa-miR-29c.

Survival analysis across three independent datasets shows that hsa-miR-29c is associated with survival in breast cancer. [2]

Targets of miR-29

The mature products are thought to exert regulatory roles by binding with partial complementarity to microRNA recognition elements (MREs) in the 3' untranslated region (3' UTR) of target transcripts. Experimental evidence suggests that putative targets of mature miR-29 products include the following:


Recently, in an attempt to identify targets at global level using Quantitative proteomics - SILAC approach, VDAC1 and VDAC2 were identified as targets of miR-29a in HEK293T cells. [8]

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.
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-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-101 microRNA precursor family

miR-101 microRNA precursor is a small non-coding RNA that regulates gene expression. Expression of miR-101 has been validated in both human and mouse. This microRNA appears to be specific to the vertebrates and has now been predicted or confirmed in a wide range of vertebrate species. The precursor microRNA is a stem-loop structure of about 70 nucleotides in length that is processed by the Dicer enzyme to form the 21-24 nucleotide mature microRNA. In this case the mature sequence is excised from the 3' arm of the hairpin.

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-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-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-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 has been predicted or experimentally confirmed in a wide number of vertebrate species such as rat, zebrafish, and pufferfish.

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.

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-126

In molecular biology mir-126 is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several pre- and post-transcription mechanisms.

mir-223 Mir-223

In molecular biology MicroRNA-223 (miR-223) is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. miR-223 is a hematopoietic specific microRNA with crucial functions in myeloid lineage development. It plays an essential role in promoting granulocytic differentiation while also being associated with the suppression of erythrocytic differentiation. miR-223 is commonly repressed in hepatocellular carcinoma and leukemia. Higher expression levels of miRNA-223 are associated with extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach and recurrent ovarian cancer. In some cancers the microRNA-223 down-regulation is correlated with higher tumor burden, disease aggressiveness, and poor prognostic factors. MicroRNA-223 is also associated with rheumatoid arthritis, sepsis, type 2 diabetes, and hepatic ischemia.

miR-191

miR-191 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.

miR-214

miR-214 is a vertebrate-specific family of microRNA precursors. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.

MicroRNA sequencing (miRNA-seq), a type of RNA-Seq, is the use of next-generation sequencing or massively parallel high-throughput DNA sequencing to sequence microRNAs, also called miRNAs. miRNA-seq differs from other forms of RNA-seq in that input material is often enriched for small RNAs. miRNA-seq allows researchers to examine tissue-specific expression patterns, disease associations, and isoforms of miRNAs, and to discover previously uncharacterized miRNAs. Evidence that dysregulated miRNAs play a role in diseases such as cancer has positioned miRNA-seq to potentially become an important tool in the future for diagnostics and prognostics as costs continue to decrease. Like other miRNA profiling technologies, miRNA-Seq has both advantages and disadvantages.

Anti-miRNA oligonucleotides have many uses in cellular mechanics. These synthetically designed molecules are used to neutralize microRNA (miRNA) function in cells for desired responses. miRNA are complementary sequences to mRNA that are involved in the cleavage of RNA or the suppression of the translation. By controlling the miRNA that regulate mRNAs in cells, AMOs can be used as further regulation as well as for therapeutic treatment for certain cellular disorders. This regulation can occur through a steric blocking mechanism as well as hybridization to miRNA. These interactions, within the body between miRNA and AMOs, can be for therapeutics in disorders in which over/under expression occurs or aberrations in miRNA lead to coding issues. Some of the miRNA linked disorders that are encountered in the humans include cancers, muscular diseases, autoimmune disorders, and viruses. In order to determine the functionality of certain AMOs, the AMO/miRNA binding expression must be measured against the expressions of the isolated miRNA. The direct detection of differing levels of genetic expression allow the relationship between AMOs and miRNAs to be shown. This can be detected through luciferase activity. Understanding the miRNA sequences involved in these diseases can allow us to use anti miRNA Oligonucleotides to disrupt pathways that lead to the under/over expression of proteins of cells that can cause symptoms for these diseases.

<span class="mw-page-title-main">MIR223</span> Non-coding RNA in the species Homo sapiens

MicroRNA 223 is a protein that in humans is encoded by the MIR223 gene.

References

  1. ↑ Ambros V (Dec 2001). "microRNAs: tiny regulators with great potential". Cell. 107 (7): 823–6. doi: 10.1016/S0092-8674(01)00616-X . PMID   11779458.
  2. ↑ Lánczky, András; Nagy, Ádám; Bottai, Giulia; Munkácsy, Gyöngyi; Szabó, András; Santarpia, Libero; Győrffy, Balázs (2016-12-01). "miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients". Breast Cancer Research and Treatment. 160 (3): 439–446. doi:10.1007/s10549-016-4013-7. ISSN   1573-7217. PMID   27744485. S2CID   11165696.
  3. ↑ Mott JL, Kobayashi S, Bronk SF, Gores GJ (Sep 2007). "mir-29 regulates Mcl-1 protein expression and apoptosis". Oncogene. 26 (42): 6133–40. doi:10.1038/sj.onc.1210436. PMC   2432524 . PMID   17404574.
  4. ↑ Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, Volinia S, Alder H, Liu CG, Rassenti L, Calin GA, Hagan JP, Kipps T, Croce CM (Dec 2006). "Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181" (PDF). Cancer Research. 66 (24): 11590–3. doi: 10.1158/0008-5472.CAN-06-3613 . PMID   17178851.
  5. ↑ Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S, Guler G, Morrison CD, Chan KK, Marcucci G, Calin GA, Huebner K, Croce CM (Oct 2007). "MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B". Proceedings of the National Academy of Sciences of the United States of America. 104 (40): 15805–10. doi: 10.1073/pnas.0707628104 . PMC   2000384 . PMID   17890317.
  6. ↑ Gebeshuber CA, Zatloukal K, Martinez J (Apr 2009). "miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis". EMBO Reports. 10 (4): 400–5. doi:10.1038/embor.2009.9. PMC   2672883 . PMID   19247375.
  7. ↑ Sanduja S, Blanco FF, Dixon DA (2011). "The roles of TTP and BRF proteins in regulated mRNA decay". Wiley Interdisciplinary Reviews: RNA. 2 (1): 42–57. doi:10.1002/wrna.28. PMC   3030256 . PMID   21278925.
  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.

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