TargetScan

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In bioinformatics, TargetScan is a web server that predicts biological targets of microRNAs (miRNAs) by searching for the presence of sites that match the seed region of each miRNA. [1] For many species, other types of sites, known as 3'-compensatory sites [1] are also identified. These miRNA target predictions are regularly updated and improved by the laboratory of David Bartel in conjunction with the Whitehead Institute Bioinformatics and Research Computing Group.[ citation needed ]

TargetScan includes TargetScanHuman, [2] [3] [4] [5] [6] TargetScanMouse, [2] [3] [4] [5] [6] TargetScanFish, [6] [7] TargetScanFly, [8] [9] and TargetScanWorm. [10] which provide predictions for mammals, zebrafish, insects, and nematodes centered on the genes of human, mouse, zebrafish, Drosophila melanogaster , and Caenorhabditis elegans , respectively.

Compared to other target-prediction tools[ which? ] TargetScan provides accurate rankings of the predicted targets for each miRNA. [6] These rankings are based on either the probability of evolutionarily conserved targeting (PCT scores. [4] ) or the predicted efficacy of repression (context++ scores). [6]

Another distinguishing feature[ compared to? ] of TargetScan is its use of extra mRNA annotations. In particular, TargetScanWorm and TargetScanFish are based on C. elegans and zebrafish mRNA models for which 3' untranslated regions (3' UTRs) are defined using polyadenylation sites that are experimentally determined using accurate high-throughput methods. [7] [10]

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

  1. Cleavage of mRNA strand into two pieces,
  2. Destabilization of mRNA by shortening its poly(A) tail, or
  3. Translation of mRNA into proteins.

Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi-subfamily Argonaute proteins. These piRNA complexes are mostly involved in the epigenetic and post-transcriptional silencing of transposable elements and other spurious or repeat-derived transcripts, but can also be involved in the regulation of other genetic elements in germ line cells.

RNA silencing or RNA interference refers to a family of gene silencing effects by which gene expression is negatively regulated by non-coding RNAs such as microRNAs. RNA silencing may also be defined as sequence-specific regulation of gene expression triggered by double-stranded RNA (dsRNA). RNA silencing mechanisms are conserved among most eukaryotes. The most common and well-studied example is RNA interference (RNAi), in which endogenously expressed microRNA (miRNA) or exogenously derived small interfering RNA (siRNA) induces the degradation of complementary messenger RNA. Other classes of small RNA have been identified, including piwi-interacting RNA (piRNA) and its subspecies repeat associated small interfering RNA (rasiRNA).

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-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-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-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-156 microRNA precursor

MicroRNA (miRNA) precursor miR156 is a family of plant non-coding RNA. This microRNA has now been predicted or experimentally confirmed in a range of plant species. Animal miRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. miR156 functions in the induction of flowering by suppressing the transcripts of SQUAMOSA-PROMOTER BINDING LIKE (SPL) transcription factors gene family. It was suggested that the loading into ARGONAUTE1 and ARGONAUTE5 is required for miR156 functionality in Arabidopsis thaliana. In plants the precursor sequences may be longer, and the carpel factory (caf) enzyme appears to be involved in processing. In this case the mature sequence comes from the 5' arm of the precursor, and both Arabidopsis thaliana and rice genomes contain a number of related miRNA precursors which give rise to almost identical mature sequences. The extents of the hairpin precursors are not generally known and are estimated based on hairpin prediction. The products are thought to have regulatory roles through complementarity to mRNA.

mir-160 microRNA precursor family

In molecular biology, mir-160 is a microRNA that has been predicted or experimentally confirmed in a range of plant species including Arabidopsis thaliana and Oryza sativa (rice). miR-160 is predicted to bind complementary sites in the untranslated regions of auxin response factor genes to regulate their expression. 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.

Mirtrons are a type of microRNAs that are located in the introns of the mRNA encoding host genes. These short hairpin introns formed via atypical miRNA biogenesis pathways. Mirtrons arise from the spliced-out introns and are known to function in gene expression.

This microRNA database and microRNA targets databases is a compilation of databases and web portals and servers used for microRNAs and their targets. MicroRNAs (miRNAs) represent an important class of small non-coding RNAs (ncRNAs) that regulate gene expression by targeting messenger RNAs.

PAR-CLIP is a biochemical method for identifying the binding sites of cellular RNA-binding proteins (RBPs) and microRNA-containing ribonucleoprotein complexes (miRNPs). The method relies on the incorporation of ribonucleoside analogs that are photoreactive, such as 4-thiouridine (4-SU) and 6-thioguanosine (6-SG), into nascent RNA transcripts by living cells. Irradiation of the cells by ultraviolet light of 365 nm wavelength induces efficient crosslinking of photoreactive nucleoside–labeled cellular RNAs to interacting RBPs. Immunoprecipitation of the RBP of interest is followed by isolation of the crosslinked and coimmunoprecipitated RNA. The isolated RNA is converted into a cDNA library and is deep sequenced using next-generation sequencing technology.

High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) is a variant of CLIP for genome-wide mapping protein–RNA binding sites or RNA modification sites in vivo. HITS-CLIP was originally used to generate genome-wide protein-RNA interaction maps for the neuron-specific RNA-binding protein and splicing factor NOVA1 and NOVA2; since then a number of other splicing factor maps have been generated, including those for PTB, RbFox2, SFRS1, hnRNP C, and even N6-Methyladenosine (m6A) mRNA modifications.

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.

In molecular biology mir-241 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-430 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-iab-4 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

David P. Bartel is an American molecular biologist best known for his work on microRNAs. Bartel is a Professor of Biology at the Massachusetts Institute of Technology, Member of the Whitehead Institute, and investigator of the Howard Hughes Medical Institute (HHMI).

References

  1. 1 2 Bartel DP (2009). "MicroRNAs: target recognition and regulatory functions". Cell. 136 (2): 215–33. doi:10.1016/j.cell.2009.01.002. PMC   3794896 . PMID   19167326.
  2. 1 2 Lewis BP, Burge CB, Bartel DP (2005). "Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets". Cell. 120 (1): 15–20. doi: 10.1016/j.cell.2004.12.035 . PMID   15652477.
  3. 1 2 Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP (2007). "MicroRNA targeting specificity in mammals: determinants beyond seed pairing". Mol. Cell. 27 (1): 91–105. doi:10.1016/j.molcel.2007.06.017. PMC   3800283 . PMID   17612493.
  4. 1 2 3 Friedman RC, Farh KK, Burge CB, Bartel DP (2009). "Most mammalian mRNAs are conserved targets of microRNAs". Genome Res. 19 (1): 92–105. doi:10.1101/gr.082701.108. PMC   2612969 . PMID   18955434.
  5. 1 2 Garcia DM, Baek D, Shin C, Bell GW, Grimson A, Bartel DP (2011). "Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs" (PDF). Nat. Struct. Mol. Biol. 18 (10): 1139–46. doi:10.1038/nsmb.2115. PMC   3190056 . PMID   21909094.
  6. 1 2 3 4 5 Agarwal, Vikram; Bell, George W.; Nam, Jin-Wu; Bartel, David P. (2015-08-12). "Predicting effective microRNA target sites in mammalian mRNAs". eLife. 4: e05005. doi: 10.7554/eLife.05005 . ISSN   2050-084X. PMC   4532895 . PMID   26267216.
  7. 1 2 Ulitsky I, Shkumatava A, Jan CH, Subtelny AO, Koppstein D, Bell GW, Sive H, Bartel DP (2012). "Extensive alternative polyadenylation during zebrafish development". Genome Res. 22 (10): 2054–66. doi:10.1101/gr.139733.112. PMC   3460199 . PMID   22722342.
  8. ↑ Ruby JG, Stark A, Johnston WK, Kellis M, Bartel DP, Lai EC (2007). "Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs". Genome Res. 17 (12): 1850–64. doi:10.1101/gr.6597907. PMC   2099593 . PMID   17989254.
  9. ↑ Agarwal, V; Subtelny, AO; Thiru, P; Ulitsky, I; Bartel, DP (4 October 2018). "Predicting microRNA targeting efficacy in Drosophila". Genome Biology. 19 (1): 152. doi: 10.1186/s13059-018-1504-3 . PMC   6172730 . PMID   30286781.
  10. 1 2 Jan CH, Friedman RC, Ruby JG, Bartel DP (2011). "Formation, regulation and evolution of Caenorhabditis elegans 3'UTRs". Nature. 469 (7328): 97–101. Bibcode:2011Natur.469...97J. doi:10.1038/nature09616. PMC   3057491 . PMID   21085120.
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