Cell-type-specific signatures of microRNAs on target mRNA expression.
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.
Center for Comparative Functional Genomics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA.
Pranidhi
P
Sood
Azra
A
Krek
Mihaela
M
Zavolan
Giuseppe
G
Macino
Nikolaus
N
Rajewsky
D020413:3' Untranslated Regions / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution
D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger