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Re-thinking miRNA-mRNA interactions: intertwining issues confound target discovery.

ABSTRACT: Despite a library full of literature on miRNA biology, core issues relating to miRNA target detection, biological effect, and mode of action remain controversial. This essay proposes that the predominant mechanism of direct miRNA action is translational inhibition, whereas the bulk of miRNA effects are mRNA based. It explores several issues confounding miRNA target detection, and discusses their impact on the dominance of "miRNA seed" dogma and the exploration of non-canonical binding sites. Finally, it makes comparisons between miRNA target prediction and transcription factor binding prediction, and questions the value of characterizing miRNA binding sites based on which miRNA nucleotides are paired with an mRNA.

SUBMITTER: Cloonan N

PROVIDER: S-EPMC4671252 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other

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Re-thinking miRNA-mRNA interactions: intertwining issues confound target discovery.

Cloonan Nicole N

BioEssays : news and reviews in molecular, cellular and developmental biology 20150212 4

Despite a library full of literature on miRNA biology, core issues relating to miRNA target detection, biological effect, and mode of action remain controversial. This essay proposes that the predominant mechanism of direct miRNA action is translational inhibition, whereas the bulk of miRNA effects are mRNA based. It explores several issues confounding miRNA target detection, and discusses their impact on the dominance of "miRNA seed" dogma and the exploration of non-canonical binding sites. Fin ...[more]

PMID: 25683051

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Project description:miRNAs are small non-coding RNAs that regulate gene expression by binding to the 3'-UTR of genes. Many recent studies have reported that miRNAs play important biological roles by regulating specific mRNAs or genes. Many sequence-based target prediction algorithms have been developed to predict miRNA targets. However, these methods are not designed for condition-specific target predictions and produce many false positives; thus, expression-based target prediction algorithms have been developed for condition-specific target predictions. A typical strategy to utilize expression data is to leverage the negative control roles of miRNAs on genes. To control false positives, a stringent cutoff value is typically set, but in this case, these methods tend to reject many true target relationships, i.e., false negatives. To overcome these limitations, additional information should be utilized. The literature is probably the best resource that we can utilize. Recent literature mining systems compile millions of articles with experiments designed for specific biological questions, and the systems provide a function to search for specific information. To utilize the literature information, we used a literature mining system, BEST, that automatically extracts information from the literature in PubMed and that allows the user to perform searches of the literature with any English words. By integrating omics data analysis methods and BEST, we developed Context-MMIA, a miRNA-mRNA target prediction method that combines expression data analysis results and the literature information extracted based on the user-specified context. In the pathway enrichment analysis using genes included in the top 200 miRNA-targets, Context-MMIA outperformed the four existing target prediction methods that we tested. In another test on whether prediction methods can re-produce experimentally validated target relationships, Context-MMIA outperformed the four existing target prediction methods. In summary, Context-MMIA allows the user to specify a context of the experimental data to predict miRNA targets, and we believe that Context-MMIA is very useful for predicting condition-specific miRNA targets.

Dataset Information

Re-thinking miRNA-mRNA interactions: intertwining issues confound target discovery.

Publications

Re-thinking miRNA-mRNA interactions: intertwining issues confound target discovery.

Similar Datasets

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