10 research outputs found
Human microRNAs preferentially target genes with intermediate levels of expression and its formation by mammalian evolution
<div><p>MicroRNAs (miRNAs) are short, endogenous RNAs that post-transcriptionally repress mRNAs. Over the course of evolution, many new miRNAs are known to have emerged and added to the existing miRNA repertoires of drosophilids and vertebrates. Despite the large number of miRNAs in existence, the complementary pairing of only ~7 bases between miRNAs and mRNAs is sufficient to induce repression. Thus, miRNA targeting is so widespread that genes coexpressed with a miRNA have evolved to avoid sites that are targeted by the miRNA. Besides this avoidance, little is known about the preferential modes of miRNA targeting. Therefore, to elucidate miRNA targeting preference and avoidance, we evaluated the bias of the number of miRNA targeting occurrences in relation to expression intensities of miRNAs and their coexpressed target mRNAs by surveying transcriptome data from human organs. We found that miRNAs preferentially target genes with intermediate levels of expression, while avoiding highly expressed ones, and that older miRNAs have greater targeting specificity, suggesting that specificity increases during the course of evolution.</p></div
Quantification of miRNA targeting specificity.
<p>Quantification of miRNA targeting specificity.</p
Outline of miRNA age and expression by age and by organ.
<p>(A) Divergence of the mammalian species/clades and the assignment of intervals of human miRNA times of origin representing the miRNA age. The intervals <i>t</i>s are 1: ante-eutherian, 2: eutherian, 3: simian, and 4: hominoid. The top horizontal line is proportional to the neutral distance [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198142#pone.0198142.ref006" target="_blank">6</a>]: the scale is shown in the upper left with a bar of 0.1 neutral substitutions per site. (B) Expression intensities of human miRNAs by organ and by miRNA age. The RNA-seq read counts of miRNAs in each human organ reported by Landgraf et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198142#pone.0198142.ref015" target="_blank">15</a>] are plotted as the base-10 logarithm against the different evolutionary ages of miRNAs: ante-eutherian (black), eutherian (blue), simian (gold), and hominoid (red).</p
Results are robust against different methods, TargetScan and PITA, with varied stringencies.
<p>Ante and Euth stand for ante-eutherian and eutherian origins of miRNAs, respectively. (AāC) Based on TargetScan-predicted sets of miRNA target sites with an increasing level of stringency, named C010, C020, and C030, the extent of miRNA targeting avoidance (avoidance index <i>A</i>) is compared between Ante (old) and Euth (younger) miRNAs. (DāF) Based on PITA-predicted sets of target sites with an increasing level of stringency, named P010, P020, and P030, the avoidance index <i>A</i> is compared between Ante and Euth miRNAs. The avoidance index of Ante is greater than that of Euth for almost all of the 10 human organs examined and over the various levels of stringency, except for (F) the PITA most stringent set P030. (GāI) TargetScan-predicted sets of C010, C020, and C030 are applied to compute preference index <i>H</i> and compare <i>H</i> between Ante and Euth miRNAs. (JāL) PITA-predicted sets of P010, P020, and P030 are applied to compare the preference index <i>H</i> between Ante and Euth miRNAs. For every plot, when the index is assigned ānot in orderā or ānot availableā, the index is plotted as ā1. <i>P</i> values are computed using the Wilcoxon signed-rank test (two-sided).</p