Dataset Information

MicroRNA modules prefer to bind weak and unconventional target sites.

ABSTRACT:

Motivation

MicroRNAs (miRNAs) play critical roles in gene regulation. Although it is well known that multiple miRNAs may work as miRNA modules to synergistically regulate common target mRNAs, the understanding of miRNA modules is still in its infancy.

Results

We employed the recently generated high throughput experimental data to study miRNA modules. We predicted 181 miRNA modules and 306 potential miRNA modules. We observed that the target sites of these predicted modules were in general weaker compared with those not bound by miRNA modules. We also discovered that miRNAs in predicted modules preferred to bind unconventional target sites rather than canonical sites. Surprisingly, contrary to a previous study, we found that most adjacent miRNA target sites from the same miRNA modules were not within the range of 10-130 nucleotides. Interestingly, the distance of target sites bound by miRNAs in the same modules was shorter when miRNA modules bound unconventional instead of canonical sites. Our study shed new light on miRNA binding and miRNA target sites, which will likely advance our understanding of miRNA regulation.

Availability and implementation

The software miRModule can be freely downloaded at http://hulab.ucf.edu/research/projects/miRNA/miRModule.

Supplementary information

Supplementary data are available at Bioinformatics online.

Contact

haihu@cs.ucf.edu or xiaoman@mail.ucf.edu.

SUBMITTER: Ding J

PROVIDER: S-EPMC4410656 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Publications

MicroRNA modules prefer to bind weak and unconventional target sites.

Ding Jun J Li Xiaoman X Hu Haiyan H

Bioinformatics (Oxford, England) 20141218 9

<h4>Motivation</h4>MicroRNAs (miRNAs) play critical roles in gene regulation. Although it is well known that multiple miRNAs may work as miRNA modules to synergistically regulate common target mRNAs, the understanding of miRNA modules is still in its infancy.<h4>Results</h4>We employed the recently generated high throughput experimental data to study miRNA modules. We predicted 181 miRNA modules and 306 potential miRNA modules. We observed that the target sites of these predicted modules were in ...[more]

PMID: 25527098

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Project description:MicroRNAs (miRNAs) control the abundance of the majority of the vertebrate transcriptome. The recognition sequences, or target sites, for bilaterian miRNAs are found predominantly in the 3' untranslated regions (3'UTRs) of mRNAs, and are amongst the most highly conserved motifs within 3'UTRs. However, little is known regarding the evolutionary pressures that lead to loss and gain of such target sites. Here, we quantify the selective pressures that act upon miRNA target sites. Notably, selective pressure extends beyond deeply conserved binding sites to those that have undergone recent substitutions. Our approach reveals that even amongst ancient animal miRNAs, which exert the strongest selective pressures on 3'UTR sequences, there are striking differences in patterns of target site evolution between miRNAs. Considering only ancient animal miRNAs, we find three distinct miRNA groups, each exhibiting characteristic rates of target site gain and loss during mammalian evolution. The first group both loses and gains sites rarely. The second group shows selection only against site loss, with site gains occurring at a neutral rate, whereas the third loses and gains sites at neutral or above expected rates. Furthermore, mutations that alter the strength of existing target sites are disfavored. Applying our approach to individual transcripts reveals variation in the distribution of selective pressure across the transcriptome and between miRNAs, ranging from strong selection acting on a small subset of targets of some miRNAs, to weak selection on many targets for other miRNAs. miR-20 and miR-30, and many other miRNAs, exhibit broad, deeply conserved targeting, while several other comparably ancient miRNAs show a lack of selective constraint, and a small number, including mir-146, exhibit evidence of rapidly evolving target sites. Our approach adds valuable perspective on the evolution of miRNAs and their targets, and can also be applied to characterize other 3'UTR regulatory motifs.

Dataset Information

MicroRNA modules prefer to bind weak and unconventional target sites.

Motivation

Results

Availability and implementation

Supplementary information

Contact

Publications

MicroRNA modules prefer to bind weak and unconventional target sites.

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