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

被引:500
作者
Sood, P
Krek, A
Zavolan, M
Macino, G
Rajewsky, N
机构
[1] NYU, Dept Biol, Ctr Comparat Funct Genom, New York, NY 10003 USA
[2] NYU, Dept Phys, New York, NY 10003 USA
[3] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland
[4] Univ Roma La Sapienza, Dipartimento Biotecnol Cellulari & Ematol, I-00161 Rome, Italy
关键词
gene expression; microarray; posttranscriptional control;
D O I
10.1073/pnas.0511045103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2746 / 2751
页数:6
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