Redirection of Silencing Targets by Adenosine-to-Inosine Editing of miRNAs

American Association for the Advancement of Science (AAAS) - Tập 315 Số 5815 - Trang 1137-1140 - 2007
Yukio Kawahara1,2,3, Boris Zinshteyn1,2,3, Praveen Sethupathy1,2, Hisashi Iizasa1,2,3, Artemis G. Hatzigeorgiou1,2, Kazuko Nishikura1,2,3
1Department of Computer and Information Science, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
2Department of Genetics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
3The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA

Tóm tắt

Primary transcripts of certain microRNA (miRNA) genes are subject to RNA editing that converts adenosine to inosine. However, the importance of miRNA editing remains largely undetermined. Here we report that tissue-specific adenosine-to-inosine editing of miR-376 cluster transcripts leads to predominant expression of edited miR-376 isoform RNAs. One highly edited site is positioned in the middle of the 5′-proximal half “seed” region critical for the hybridization of miRNAs to targets. We provide evidence that the edited miR-376 RNA silences specifically a different set of genes. Repression of phosphoribosyl pyrophosphate synthetase 1, a target of the edited miR-376 RNA and an enzyme involved in the uric-acid synthesis pathway, contributes to tight and tissue-specific regulation of uric-acid levels, revealing a previously unknown role for RNA editing in miRNA-mediated gene silencing.

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Tài liệu tham khảo

10.1016/S0092-8674(04)00045-5

10.1242/dev.02070

10.1016/j.gde.2005.12.005

10.1038/nrg1379

10.1038/nrm1644

10.1186/gb-2006-7-4-r27

10.1261/rna.7350304

10.1038/nsmb1041

10.1101/gr.2743304

10.1038/nature03076

Materials and methods are available as supporting material on Science Online.

10.1146/annurev.biochem.71.110601.135501

10.1038/nrm2061

10.1016/S0168-9525(00)02169-7

10.1016/S0896-6273(02)00760-2

10.1038/35017558

10.1074/jbc.M311347200

10.1074/jbc.M310162200

10.1074/jbc.274.11.7482

10.1038/nmeth746

This work was supported in part by grants from NIH the Juvenile Diabetes Research Foundation the Commonwealth Universal Research Enhancement Program and the Pennsylvania Department of Health (K.N.); and by a grant from NSF (AG.H.). P.S. is also supported by a predoctoral NIH training grant. We thank M. Higuchi and P. H. Seeburg for ADAR2 –/– mice Q. Wang for mouse embryo RNAs Z. Mourelatos and J. M. Murray for reading and comments and S. Lui and U. Samala for technical assistance.

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American Association for the Advancement of Science (AAAS)

Tập 315 Số 5815

1137-1140

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