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

Proceedings of the National Academy of Sciences of the United States of America - Tập 103 Số 8 - Trang 2746-2751 - 2006
Pranidhi Sood1, Azra Krek2,3, Mihaela Zavolan4, Giuseppe Macino5,6, Nikolaus Rajewsky2
1Center for Comparative Functional Genomics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA.
2*Center for Comparative Functional Genomics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003;
3Department of Physics, New York University, 4 Washington Place, New York, NY 10003;
4Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland; and
5Cellular Biotechnologies and Hematology
6Dipartimento di Biotecnologie Cellulari ed Ematologia, Universita di Roma La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy

Tóm tắt

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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Proceedings of the National Academy of Sciences of the United States of America

Tập 103 Số 8

2746-2751

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