Analyzing mRNA expression identifies Smad3 as a microRNA-140 target regulated only at protein level

Pais, H, Nicolas, FE, Soond, S, Swingler, T, Clark, I, Chantry, A, Moulton, V and Dalmay, T (2010) Analyzing mRNA expression identifies Smad3 as a microRNA-140 target regulated only at protein level. RNA, 16 (3). pp. 489-494. ISSN 1355-8382

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Abstract

mRNA profiling is routinely used to identify microRNA targets, however, this high-throughput technology is not suitable for identifying targets regulated only at protein level. Here, we have developed and validated a novel methodology based on computational analysis of promoter sequences combined with mRNA microarray experiments to reveal transcription factors that are direct microRNA targets at the protein level. Using this approach we identified Smad3, a key transcription factor in the TGFß signaling pathway, as a direct miR-140 target. We showed that miR-140 suppressed the TGFß pathway through repression of Smad3 and that TGFß suppressed the accumulation of miR-140 forming a double negative feedback loop. Our findings establish a valid strategy for the discovery of microRNA targets regulated only at protein level, and we propose that additional targets could be identified by re-analysis of existing microarray datasets.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Science > School of Computing Sciences
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Depositing User: Users 2731 not found.
Date Deposited: 08 Mar 2011 10:39
Last Modified: 21 Apr 2020 17:04
URI: https://ueaeprints.uea.ac.uk/id/eprint/25726
DOI: 10.1261/rna.1701210

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