Abstract

<p><b>(A)</b> Minimal overlap between ribo-upregulated TKO targets and ribo-downregulated TG targets. <b>(B-D)</b> The responses of ribosome density of ribo-upregulated TKO targets <b>(B)</b> and ribo-downregulated TG targets <b>(C)</b> to three miR-17~92 expression levels. Translated genes lacking miR-17~92 binding sites were used as control <b>(D)</b>. Colored bars indicate median values and error bars represent interquartile ranges. Each dot represents relative ribosome density of a unique gene. Numbers indicate p-values. <b>(E)</b> Different sensitivity of individual target genes to miR-17~92 expression level changes. Protein levels were determined by immunoblot and normalized to β-Actin (<b><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006623#pgen.1006623.s007" target="_blank">S7</a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006623#pgen.1006623.s011" target="_blank">S11</a> Figs</b>). Target gene protein levels in WT B cells were arbitrarily set as 1.0 (n≥4). Vertical lines indicate error bars. <b>(F)</b> Relative mRNA levels of individual target genes in TKO, WT and TG B cells as determined by microarray (n = 3). <b>(G)</b> A hypothetical curve depicting target gene protein level change as a function of miRNA concentration. For a miRNA-target mRNA interaction in a given cellular context, there are a threshold level and a saturation level of miRNA concentration. miRNA suppresses target gene expression in a dose-dependent manner when miRNA concentration is between the threshold and saturation levels. Suppression does not occur when miRNA concentration is below the threshold level, while suppression reaches a maximal when miRNA concentration is above the saturation level. <b>(H)</b> The hypothetical response curves of group1, group2 and group3 target genes to miR-17~92 expression level changes. Note that the difference in amplitude for individual target genes is not depicted in this graph.</p

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