Cell-type-specific signatures of microRNAs on target mRNA expression - PubMed (original) (raw)

Cell-type-specific signatures of microRNAs on target mRNA expression

Pranidhi Sood et al. Proc Natl Acad Sci U S A. 2006.

Abstract

Although it is known that the human genome contains hundreds of microRNA (miRNA) genes and that each miRNA can regulate a large number of mRNA targets, the overall effect of miRNAs on mRNA tissue profiles has not been systematically elucidated. Here, we show that predicted human mRNA targets of several highly tissue-specific miRNAs are typically expressed in the same tissue as the miRNA but at significantly lower levels than in tissues where the miRNA is not present. Conversely, highly expressed genes are often enriched in mRNAs that do not have the recognition motifs for the miRNAs expressed in these tissues. Together, our data support the hypothesis that miRNA expression broadly contributes to tissue specificity of mRNA expression in many human tissues. Based on these insights, we apply a computational tool to directly correlate 3' UTR motifs with changes in mRNA levels upon miRNA overexpression or knockdown. We show that this tool can identify functionally important 3' UTR motifs without cross-species comparison.

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Conflict of interest statement

Conflict of interest statement: No conflicts declared.

Figures

Fig. 1.

Fig. 1.

Cell-type-specific signatures of miRNAs on target mRNA expression. Shown is analysis of the mRNA expression of predicted targets for three highly tissue-specific miRNAs across 79 human tissues (miR-122, miR-1, and miR-7). Negative values (“scores”; y axis) indicate the significance of predicted miRNA targets to be expressed at lower levels in a tissue relative to all other tissues, compared with a background set of mRNAs (gene-centric analysis; see Methods). Analogously, positive values reflect the significance of miRNA targets to be expressed at high levels compared with other tissues. Tissues are sorted by these scores. Arrows indicate the tissue in which the miRNA is expressed.

Fig. 2.

Fig. 2.

The enrichment/depletion of predicted miRNA targets in highly/lowly expressed mRNAs is tissue-specific. (A) Number of transcripts predicted to be targeted by miRNAs (y axis) as a function of the top n specifically highly expressed genes (x axis) for three neuronal and four nonneuronal tissues. (B) Analogously, number of transcripts predicted to be targeted by miRNAs as a function of the top n specifically lowly expressed genes for three neuronal and four nonneuronal tissues.

Fig. 3.

Fig. 3.

The average 3′ UTR length of highly specifically expressed mRNAs is tissue-specific. Shown, for each tissue, is the average 3′ UTR length in nucleotides of the top 200 most highly specifically expressed mRNAs (blue curve). Tissues are sorted by these average 3′ UTR lengths. As a control, the average 3′ UTR lengths of 200 genes that were expressed at average levels in each tissue are also shown (red curve).

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