Prediction of mammalian microRNA targets.

By Benjamin P. Lewis, I. Shih, M. Jones-Rhoades, David P. Bartel, C. Burge. Cell, 2003

5,372 citations recorded by the source corpus.

MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes, insects, and plants by basepairing to mRNAs to specify posttranscriptional repression of these messages. However, the mRNAs regulated by vertebrate miRNAs are all unknown. Here we predict more than 400 regulatory target genes for the conserved vertebrate miRNAs by identifying mRNAs with conserved pairing to the 5' region of the miRNA and evaluating the number and quality of these complementary sites. Rigorous tests using shuffled miRNA controls supported a majority of these predictions, with the fraction of false positives estimated at 31% for targets identified in human, mouse, and rat and 22% for targets identified in pufferfish as well as mammals. Eleven predicted targets (out of 15 tested) were supported experimentally using a HeLa cell reporter system. The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c81a5f7469419748daff6272230ed330001ee8f2

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Citations in the corpus

High-Throughput Sequencing of Arabidopsis microRNAs: Evidence for Frequent Birth and Death of MIRNA Genes (2007, background): “In humans, for example, computational and indirect experimental evidence indicates that miRNAs regulate expression of up to 1/3 of all genes [14–17].”
Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity. (2017, positive): “These miRNAs contain 6- to 8-nucleotide seed sequences, which correspond to complementary sequences in the 30 UTR of target mRNAs (Brennecke et al., 2005; Lewis et al., 2003, 2005).”
MicroRNA biogenesis: coordinated cropping and dicing (2005, background): “For example, a single miRNA can bind to and regulate many different mRNA targets and, conversely, several different miRNAs can bind to and cooperatively control a single mRNA targe”
Transcripts Targeted by the MicroRNA-16 Family Cooperatively Regulate Cell Cycle Progression (2007, methodology): “Computational methods have been used to predict human miRNA targets (31, 34, 37 , 45, 52).”
Tools for Sequence-Based miRNA Target Prediction: What to Choose? (2016, methodology): “79 conserved mammalian miRNAs extracted from Rfam [44].”
microRNAs in cancer (2013, methodology): “The algorithms based on conservation criteria include miRanda (27), PicTar (28), TargetScan (29), and DIANA-microT (30).”
MicroRNA targeting specificity in mammals: determinants beyond seed pairing. (2007, methodology): “However , when we used previously developed energy-based rubrics for predicting and scoring 3 0 supplementary pairing (Lewis et al., 2003; John et al., 2004; Krek et al., 2005), those sites with better scores were no more effective ; indeed, increased supplementary pairing, as measured by these…”
Identifying miRNAs, targets and functions (2012, methodology): “[36] and PicTar [49], which restrict their predictions primarily to conserved sites in 30-UTRs, were reported to nevertheless have false-positive rates of”
TarBase: A comprehensive database of experimentally supported animal microRNA targets. (2005, methodology): “We must emphasize, however, that machine-learning methods for target prediction are not necessarily superior to approaches that do not employ training sets (Lewis et al. 2003, 2005; Krek al.”