Functional microRNA targets in protein coding sequences

Reczko, Martin; Maragkakis, Manolis; Alexiou, Panagiotis; Große, Ivo; Hatzigeorgiou, Artemis G.

doi:10.1093/bioinformatics/bts043

Cited by 472 publications

(435 citation statements)

References 33 publications

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“…Changing the length of the 3 0 UTR is believed to affect the stability, localization, transport, and even translation of the mRNA through altered interactions with microRNAs or other regulatory RNA binding proteins. [28][29][30][31][32] Several polyadenylation factors have been implicated in APA including CF1m 33,34 and CstF. 35,36 For example, knockdown of CF1m25 (CF1m25 KD) or CstF64 (CstF64 KD) has been shown to result in the activation of alternative poly(A) sites.…”

Section: Introductionmentioning

confidence: 99%

Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns

et al. 2016

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Alternative polyadenylation has been implicated as an important regulator of gene expression. In some cases, alternative polyadenylation is known to couple with alternative splicing to influence last intron removal. However, it is unknown whether alternative polyadenylation events influence alternative splicing decisions at upstream exons. Knockdown of the polyadenylation factors CFIm25 or CstF64 in HeLa cells was used as an approach in identifying alternative polyadenylation and alternative splicing events on a genome-wide scale. Although hundreds of alternative splicing events were found to be differentially spliced in the knockdown of CstF64, genes associated with alternative polyadenylation did not exhibit an increased incidence of alternative splicing. These results demonstrate that the coupling between alternative polyadenylation and alternative splicing is usually limited to defining the last exon. The striking influence of CstF64 knockdown on alternative splicing can be explained through its effects on UTR selection of known splicing regulators such as hnRNP A2/B1, thereby indirectly influencing splice site selection. We conclude that changes in the expression of the polyadenylation factor CstF64 influences alternative splicing through indirect effects.

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Section: Introductionmentioning

confidence: 99%

Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns

et al. 2016

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“…In silico analysis was performed to identify miRNA target genes and molecular pathways potentially altered by the expression of single or multiple miRNAs. Putative target genes of miRNA were determined using the homology search algorithm microT-CDS and a database of published, experimentally validated miRNA-gene interactions, TarBase (42,43). For microT-CDS, a microT prediction threshold of >0.8 was set.…”

Section: Methodsmentioning

confidence: 99%

Circulating microRNA signature for the diagnosis of very high-risk prostate cancer

Alhasan

Scott

et al. 2016

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

125

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We report the identification of a molecular signature using the Scano-miR profiling platform based on the differential expression of circulating microRNAs (miRNA, miR) in serum samples specific to patients with very high-risk (VHR) prostate cancer (PCa). Five miRNA PCa biomarkers (miR-200c, miR-605, miR-135a*, miR-433, and miR-106a) were identified as useful for differentiating indolent and aggressive forms of PCa. All patients with VHR PCa in the study had elevated serum levels of miR-200c. Circulating miR-433, which was differentially expressed in patients with VHR versus low-risk (LR) forms of PCa, was not detectable by quantitative real-time PCR in samples from healthy volunteers. In blind studies, the five miRNA PCa biomarkers were able to differentiate patients with VHR PCas from those with LR forms as well as healthy individuals with at least 89% accuracy. Biological pathway analysis showed the predictive capability of these miRNA biomarkers for the diagnosis and prognosis of VHR aggressive PCa.

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“…For the template network construction, i.e., miRNA-mRNA target relationship, we used both experimentally validated CLASH (Helwak et al, 2013) data, and a computationally predicted database, doRiNA (Anders et al, 2011) that is an unified databases containing CLASH experiments, TargetScan (Lewis et al, 2005), and PicTar (Kret et al, 2005). We further extended the target relationships by manually curated several databases -PITA (Kertesz et al, 2007), miRTarBase (Hsu et al, 2010), and DIANA-micro-T (Xu et al, 2014;Reczko et al, 2012).…”

Section: Materials and Datamentioning

confidence: 99%

“…Typically, methods in the second category use machine learning techniques and experimentally verified target pairs as training data. DIANA-microT (Xu et al, 2014;Reczko et al, 2012) is one of the algorithms in the second category. Tools in the third category are to detect condition-specific target relationships between miRNAs and genes.…”

Section: Introductionmentioning

confidence: 99%

Iterative segmented least square method for functional microRNA-mRNA module discovery in breast cancer

Rhee

Lim

Kim

2017

IJDMB

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MicroRNAs (miRNAs) have significant biological roles at the molecular level by regulating genes post-transcriptionally. To understand the functional effects of miRNAs in different biological contexts, it is essential to elucidate miRNA-mRNA regulatory modules (MRMs). The computational complexity for inferencing MRMs is very high due to the many-to-many relationships between miRNAs and mRNAs and inferencing MRMs is still a challenging unresolved problem. In this paper, we propose a novel iterative segmented least square method for functional MRM discovery. Our method operates in two steps: (a) grouping and ordering the miRNAs and mRNAs to build per-sample matrices representing miRNA-mRNA regulations, and (b) determining maximum sized modules from structured miRNA-mRNA matrices. In experiments with human breast cancer data sets from TCGA, we show that our method outperforms existing methods in terms of both GO similarity and cluster evaluation. In addition, we show that modules determined by our method can be used for breast cancer survival prediction and subtype classification.

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Functional microRNA targets in protein coding sequences

Cited by 472 publications

References 33 publications

Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns

Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns

Circulating microRNA signature for the diagnosis of very high-risk prostate cancer

Iterative segmented least square method for functional microRNA-mRNA module discovery in breast cancer

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