A Genome-Wide Map of Conserved MicroRNA Targets in C. elegans

Lall, Sabbi; Grün, Dominic; Krek, Azra; Chen, Kevin; Wang, Yi Lu; Dewey, Colin N.; Sood, Pranidhi; Colombo, Teresa; Bray, Nicolas; MacMenamin, Philip; Kao, Huey Ling; Gunsalus, Kristin C.; Pachter, Lior; Piano, Fabio; Rajewsky, Nikolaus

doi:10.1016/j.cub.2006.01.050

Cited by 384 publications

(322 citation statements)

References 63 publications

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“…We observed overall similar results with this method but found that many seeds did not generate sizable control seeds that satisfied the tolerance for frequency in the transcriptome. We therefore preferred the former strategy, which has been used in several target studies in various animal clades Krek et al 2005;Lall et al 2006).…”

Section: Analysis Of Conserved Target Propertiesmentioning

confidence: 99%

Widespread regulatory activity of vertebrate microRNA* species

Yang

Phillips

Betel

et al. 2010

RNA

315

242

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An obligate intermediate during microRNA (miRNA) biogenesis is an~22-nucleotide RNA duplex, from which the mature miRNA is preferentially incorporated into a silencing complex. Its partner miRNA* species is generally regarded as a passenger RNA, whose regulatory capacity has not been systematically examined in vertebrates. Our bioinformatic analyses demonstrate that a substantial fraction of miRNA* species are stringently conserved over vertebrate evolution, collectively exhibit greatest conservation in their seed regions, and define complementary motifs whose conservation across vertebrate 39-UTR evolution is statistically significant. Functional tests of 22 miRNA expression constructs revealed that a majority could repress both miRNA and miRNA* perfect match reporters, and the ratio of miRNA:miRNA* sensor repression was correlated with the endogenous ratio of miRNA:miRNA* reads. Analysis of microarray data provided transcriptome-wide evidence for the regulation of seedmatched targets for both mature and star strand species of several miRNAs relevant to oncogenesis, including mir-17, mir-34a, and mir-19. Finally, 39-UTR sensor assays and mutagenesis tests confirmed direct repression of five miR-19* targets via star seed sites. Overall, our data demonstrate that miRNA* species have demonstrable impact on vertebrate regulatory networks and should be taken into account in studies of miRNA functions and their contribution to disease states.

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Section: Analysis Of Conserved Target Propertiesmentioning

confidence: 99%

Widespread regulatory activity of vertebrate microRNA* species

Yang

Phillips

Betel

et al. 2010

RNA

315

242

View full text Add to dashboard Cite

show abstract

“…Using the algorithms for target gene prediction, including PicTar (Lall et al, 2006), TargetScan (Lewis et al, 2003), and miRanda (John et al, 2004), the key enzyme in DNA methylation, DNMT3A, was identified as one of the potential targets of miR-143. The predicted binding of miR-143 with DNMT3A 3 0 UTR is illustrated in Figure 2A.…”

Section: In Silico Prediction Of Mir-143 Targetmentioning

confidence: 99%

MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer

et al. 2009

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BACKGROUND: MicroRNAs (miRNAs) are 19-25-nucleotides regulatory non-protein-coding RNA molecules that regulate the expressions of a wide variety of genes, including some involved in cancer development. In this study, we investigated the possible role of miR-143 in colorectal cancer (CRC). METHODS: Expression levels of human mature miRNAs were examined using real-time PCR-based expression arrays on paired colorectal carcinomas and adjacent non-cancerous colonic tissues. The downregulation of miR-143 was further evaluated in colon cancer cell lines and in paired CRC and adjacent non-cancerous colonic tissues by qRT -PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was investigated in human colon cancer cell lines to confirm miRNA -target association. RESULTS: Both real-time PCR-based expression arrays and qRT -PCR showed that miR-143 was frequently downregulated in 87.5% (35 of 40) of colorectal carcinoma tissues compared with their adjacent non-cancerous colonic tissues. Using in silico predictions, DNA methyltranferase 3A (DNMT3A) was defined as a potential target of miR-143. Restoration of the miR-143 expression in colon cell lines decreased tumour cell growth and soft-agar colony formation, and downregulated the DNMT3A expression in both mRNA and protein levels. DNMT3A was shown to be a direct target of miR-143 by luciferase reporter assay. Furthermore, the miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in CRC tissues. CONCLUSION: Our findings suggest that miR-143 regulates DNMT3A in CRC. These findings elucidated a tumour-suppressive role of miR-143 in the epigenetic aberration of CRC, providing a potential development of miRNA-based targeted approaches for CRC therapy.

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“…Another function of the 3 0 region of a miRNA is to give specificity to the members of miRNA families that share identical seeds but they diverge in their 3 0 sequences (Brennecke et al, 2005). The recognition of the principles of miRNA targeting accelerated the development and improvement of a series of bio-computational approaches to predict miRNA targets in animals that produced a remarkably large number of putative miRNA-regulated transcripts further emphasizing the significance of miRNAs (Enright et al, 2003;Stark et al, 2003;Kiriakidou et al, 2004;Lewis et al, 2005;Lall et al, 2006).…”

Section: Mechanism(s) Of Mirna-mediated Gene Regulationmentioning

confidence: 99%

Principles and effects of microRNA-mediated post-transcriptional gene regulation

2006

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MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of many key biological processes. Recent advances in understanding the mechanism of RNA interference and miRNA-mediated mechanisms shed light on major principals of the formation of the regulatory complex and provide models to explain how these small regulatory RNA species interfere with gene expression and how they influence the translational status of the transcriptome.

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A Genome-Wide Map of Conserved MicroRNA Targets in C. elegans

Cited by 384 publications

References 63 publications

Widespread regulatory activity of vertebrate microRNA* species

Widespread regulatory activity of vertebrate microRNA* species

MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer

Principles and effects of microRNA-mediated post-transcriptional gene regulation

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