RNAhybrid: microRNA target prediction easy, fast and flexible

Kruger, Jan Walters; Rehmsmeier, Marc

doi:10.1093/nar/gkl243

Cited by 1,559 publications

(1,207 citation statements)

References 23 publications

Supporting

Mentioning

1,154

Contrasting

Unclassified

Order By: Relevance

“…3C). Next, we cloned six different experimentally verified miR-21 target sites with various predicted binding free energies (20) into the 3′-UTR of ceRNA2 (EYFP-expressing construct), respectively (Figs. 2B and 3D).…”

Section: Resultsmentioning

confidence: 99%

Model-guided quantitative analysis of microRNA-mediated regulation on competing endogenous RNAs using a synthetic gene circuit

Yuan

Liu

Xie

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

108

104

View full text Add to dashboard Cite

Competing endogenous RNAs (ceRNAs) cross-regulate each other at the posttranscriptional level by titrating shared microRNAs (miRNAs). Here, we established a computational model to quantitatively describe a minimum ceRNA network and experimentally validated our model predictions in cultured human cells by using synthetic gene circuits. We demonstrated that the range and strength of ceRNA regulation are largely determined by the relative abundance and the binding strength of miRNA and ceRNAs. We found that a nonreciprocal competing effect between partially and perfectly complementary targets is mainly due to different miRNA loss rates in these two types of regulations. Furthermore, we showed that miRNA-like off targets with high expression levels and strong binding sites significantly diminish the RNA interference efficiency, but the effect caused by high expression levels could be compensated by introducing more small interference RNAs (siRNAs). Thus, our results provided a quantitative understanding of ceRNA cross-regulation via shared miRNA and implied an siRNA design strategy to reduce the siRNA off-target effect in mammalian cells. RNAs that are loaded onto RNA-induced silencing complexes (RISC) and subsequently bind to their target RNAs. In mammalian cells, the perfect pairing of miRNA to target RNAs causes RNA cleavage through the RNA interference (RNAi) pathway, whereas partial pairing results in translational repression and RNA destabilization (1, 2). miRNA-mediated regulation can be triggered by only 6-nt complementarity of the miRNA 5′-end "seed region" to the target RNA, which confers each miRNA species the capacity to interact with multiple RNA species, including gene-coding mRNAs (3, 4), long noncoding RNAs (5), and circular RNAs (6). Similarly, each RNA species can interact with multiple miRNA species through various miRNA response elements (MREs) (7).The complex interaction network of miRNAs and their target RNAs has been shown to allow indirect cross-regulation between different competing endogenous RNAs (ceRNAs) by sequestering shared miRNAs, which is essential for regulating many biological functions (7). The strength of ceRNA regulation is largely determined by the relative abundance and binding strength of ceRNAs and miRNAs and whether the miRNA-bound ceRNA decays through a stoichiometric mechanism or a catalytic mechanism (8-10). The threshold-like behavior of the ceRNA regulation has been experimentally observed by measuring the abundance of two ceRNAs, phosphatase and tensin homolog (PTEN) and vesicle-associated membrane protein (VAMP)-associated protein A (VAPA) across various cell lines (8). Nevertheless, many quantitative predictions deduced from miRNA-ceRNA computational models have not been experimentally validated. Another intriguing question is whether the miRNA-mediated catalytic mechanism can be affected by the miRNA-mediated stoichiometric mechanism through a ceRNA effect or vice versa.Currently, the ability to systematically elucidate features of the ceRNA effect is impeded by th...

show abstract

Section: Resultsmentioning

confidence: 99%

Model-guided quantitative analysis of microRNA-mediated regulation on competing endogenous RNAs using a synthetic gene circuit

Yuan

Liu

Xie

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

108

104

View full text Add to dashboard Cite

show abstract

“…Conservation and phylogenetic analyses were done by the publicly available WebLogo, a sequence logo generator (Larkin et al, 2007), and ClustalW (Crooks et al, 2004) to generate a cladogram tree using neighborjoining clustering, respectively. For data mining in the identification of miRNAs' targets, psRNATarget, a plant small RNA target analysis server available at http:// plantgrn.noble.org/psRNATarget/ (Dai and Zhao, 2011), and RNAhybrid, a miRNA target prediction tool (bibiserv2.cebitec.uni-bielefeld.de/rnahybrid) (Kruger and Rehmsmeier, 2006), were used. The GO database was downloaded from the Gene Ontology website (http:// www.geneontology.org/GO.downloads.shtml) for the confirmation of miRNAs' functions.…”

Section: Bioinformatics Tools Used For Prediction Of Mirnasmentioning

confidence: 99%

Bioinformatics profiling and characterization of potentialmicroRNAs and their targets in the genus Coffea

Bibi¹,

Barozai²,

Din³

2017

Turk J Agric For

View full text Add to dashboard Cite

IntroductionMicroRNAs (miRNAs) are an extensive class of noncoding small endogenous RNAs of 18 to 26 nt in length that are derived from self-complementary fold-back structures of longer precursor sequences (pre-miRNAs) and are generated by Dicer-like 1 (DCL1) in plants (Bartel, 2004). Mature miRNAs inhibit gene expression at posttranscriptional levels by either targeting mRNAs for degradation or inhibiting protein translation. Both processes are accomplished by the complementary base pairing of miRNAs to their target mRNA sequences (Ambros, 2004). In plants, for a majority of cases, miRNAs interact with their targets through perfect or near-perfect base pairing and lead to target mRNA degradation (Jones-Rhoades et al., 2006). Increasing evidence has revealed that miRNAs play an important role in a wide range of development processes in plants, including cell proliferation, stress response, metabolism, inflammation, and signal transduction (Ambros, 2004;Jones-Rhoades et al., 2006;Zhang et al., 2007a;Ali et al., 2016) and crosskingdom gene regulation (Barozai and Din, 2017). To date, more than 28,645 miRNAs have been identified from 223 species of plants and animals and deposited in the publicly available database miRBase (Release 21) (Griffiths-Jones et al., 2008). The majority of plant miRNAs have been found in species with fully sequenced genomes including 713 from Oryza sativa, 401 from Populus trichocarpa, 384 from Arabidopsis thaliana, 343 from Solanum tuberosum, 321 from Zea mays, and 241 from Sorghum bicolor (Griffiths-Jones et al., 2008). miRNA-related research is continuously growing and miRNAs, along with their functions, are being identified and elucidated using a wide variety of computational tools and experimental methods including direct cloning, deep sequencing, and other approaches. Comparison of miRNAs across multiple plant species has demonstrated that some miRNAs are highly evolutionary conserved from species to species, such as from mosses to higher flowering eudicots in the plant kingdom (Floyd and Bowman, 2004;Zhang et al., 2006aZhang et al., , 2006b. Conservation of miRNA sequences has provided a powerful strategy for identifying miRNAs in other species. Currently, comparative genome-based homolog searches have been used to identify conserved miRNAs in many plant species, including cotton (

show abstract

“…To identify the putative gene targets of miR-8, we took an in silico approach, as previously described (8), using five different targetprediction programs: TargetScan (14), PITA (15), miRanda (16), RNAhybrid (17), and a program developed in house (8). To assess conservation criteria, we predicted miR-8 targets using Ae.…”

Section: Mir-8 Is Enriched In the Female Mosquito Fat Body After Bloodmentioning

confidence: 99%

MicroRNA-8 targets the Wingless signaling pathway in the female mosquito fat body to regulate reproductive processes

Lucas

Roy

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

View full text Add to dashboard Cite

Female mosquitoes require a blood meal for reproduction, and this blood meal provides the underlying mechanism for the spread of many important vector-borne diseases in humans. A deeper understanding of the molecular mechanisms linked to mosquito blood meal processes and reproductive events is of particular importance for devising innovative vector control strategies. We found that the conserved microRNA miR-8 is an essential regulator of mosquito reproductive events. Two strategies to inhibit miR-8 function in vivo were used for functional characterization: systemic antagomir depletion and spatiotemporal inhibition using the miRNA sponge transgenic method in combination with the yeast transcriptional activator gal4 protein/upstream activating sequence system. Depletion of miR-8 in the female mosquito results in defects related to egg development and deposition. We used a multialgorithm approach for miRNA target prediction in mosquito 3′ UTRs and experimentally verified secreted winglessinteracting molecule (swim) as an authentic target of miR-8. Our findings demonstrate that miR-8 controls the activity of the longrange Wingless (Wg) signaling by regulating Swim expression in the female fat body. We discovered that the miR-8/Wg axis is critical for the proper secretion of lipophorin and vitellogenin by the fat body and subsequent accumulation of these yolk protein precursors by developing oocytes.small RNA | microRNA | Wingless signaling | reproduction | mosquito

show abstract

RNAhybrid: microRNA target prediction easy, fast and flexible

Cited by 1,559 publications

References 23 publications

Model-guided quantitative analysis of microRNA-mediated regulation on competing endogenous RNAs using a synthetic gene circuit

Model-guided quantitative analysis of microRNA-mediated regulation on competing endogenous RNAs using a synthetic gene circuit

Bioinformatics profiling and characterization of potentialmicroRNAs and their targets in the genus Coffea

MicroRNA-8 targets the Wingless signaling pathway in the female mosquito fat body to regulate reproductive processes

Contact Info

Product

Resources

About