Phylogenetic shadowing and computational identification of human microRNA genes.

By Eugene Berezikov, V. Guryev, J. Belt, Erno Wienholds, Ronald H. A. Plasterk, Edwin Cuppen. Cell, 2005

1,346 citations recorded by the source corpus.

We sequenced 122 miRNAs in 10 primate species to reveal conservation characteristics of miRNA genes. Strong conservation is observed in stems of miRNA hairpins and increased variation in loop sequences. Interestingly, a striking drop in conservation was found for sequences immediately flanking the miRNA hairpins. This characteristic profile was employed to predict novel miRNAs using cross-species comparisons. Nine hundred and seventy-six candidate miRNAs were identified by scanning whole-genome human/mouse and human/rat alignments. Most of the novel candidates are conserved also in other vertebrates (dog, cow, chicken, opossum, zebrafish). Northern blot analysis confirmed the expression of mature miRNAs for 16 out of 69 representative candidates. Additional support for the expression of 179 novel candidates can be found in public databases, their presence in gene clusters, and literature that appeared after these predictions were made. Taken together, these results suggest the presence of significantly higher numbers of miRNAs in the human genome than previously estimated.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1c340ae9a0ef995a2902226c3e2806a831519a25

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Citations in the corpus

MicroRNA functions in animal development and human disease (2005, background): “And in early Dicer1 mutant mouse embryos, the pool of pluripotent stem cells that is required for the proliferation of cells in the inner cell mass of the blastocyst is diminished, as assayed by in situ hybridization using probes against Oct4 mRNA (Bernstein et al., 2001).”
Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. (2010, methodology): “…indicating that additional pan-mammalian gene families remain to be found, although we have no evidence supporting the idea that the number of conserved gene families will rise to the very high levels suggested by some earlier computational studies (Berezikov et al. 2005, 2006b; Xie et al. 2005).”
Increased MicroRNA-1 and MicroRNA-133a Levels in Serum of Patients With Cardiovascular Disease Indicate Myocardial Damage (2011, background): “Discussion We report that (1) the levels of circulating miR-1 and miR-133a are elevated early after the onset of chest pain when there was no elevation in CPK or cTnT, (2) elevated levels of miR-133a were also observed in patients with UAP and Takotsubo cardiomyopathy, (3) miRNA microarray analysis ”
Identification of hundreds of conserved and nonconserved human microRNAs (2005, result): “Bioinformatic predictions of conserved microRNAs published after we obtained our results include 32 of these 36 conserved microRNAs (12 appear in the 958 predictions of Berezikov et al”
TarBase: A comprehensive database of experimentally supported animal microRNA targets. (2005, background): “It is now reported that miRNAs constitute anywhere from ~ 1% (Lim et al. 2003; Bartel 2004) to ~ 3% ( Bentwich et al. 2005; Berezikov et al. 2005 of the known genes in eukaryotes.”
miRanalyzer: a microRNA detection and analysis tool for next-generation sequencing experiments (2009, methodology): “Some of the methods used in the purely computational detection approaches were, for example, conservation of certain regions—phylogenetic shadowing (8), different machine learning methods like support vector machines using structure-sequence features (9), random forest models (10) or probabilistic c”
The Emerging Paradigm of Network Medicine in the Study of Human Disease (2012, background): “29–31 It is estimated that most messenger RNA transcripts are regulated by miRNA, 32,33 with each miRNA ( (cid:2) 700 identified mammalian miRNA) typically repressing expression of multiple mRNA (at times, (cid:2) 100 targets simultaneously).”
MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer (2008, background): “MicroRNAs (miRNAs) have been discovered as naturally occuring non-coding RNAs, controlling gene expression via specific sites at the 30-UTR of target-mRNAs, causing translational repression or degradation (Berezikov et al., 2005; Pillai et al., 2005; Zamore and Haley, 2005).”
MicroRNA Expression Signature and Antisense-Mediated Depletion Reveal an Essential Role of MicroRNA in Vascular Neointimal Lesion Formation (2007, methodology): “dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method as described (9).”
Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma (2009, background): “It is estimated that approximately 1,000 miRNAs exist in the vertebrate genome.(2) So far, 695 human miRNAs are registered at miRBase release 11.”
miREvo: an integrative microRNA evolutionary analysis platform for next-generation sequencing experiments (2012, background): “In fact, the strong phylogenetic conservation has been a wildly-used criterion for the identification of miRNAs, such as in Arabidopsis thaliana [7] and human [8].”