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Nucleic Acids Research 2005 33(8):2697-2706; doi:10.1093/nar/gki567
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Published online 12 May 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

Clustering and conservation patterns of human microRNAs

Yael Altuvia, Pablo Landgraf1, Gila Lithwick, Naama Elefant, Sébastien Pfeffer1, Alexei Aravin1, Michael J. Brownstein2, Thomas Tuschl1 and Hanah Margalit*

Department of Molecular Genetics and Biotechnology, Faculty of Medicine, The Hebrew University PO Box 12272, Jerusalem 91120, Israel 1Laboratory of RNA Molecular Biology, The Rockefeller University 1230 York Avenue, Box 186, New York, NY 10021, USA 2Laboratory of Genetics NIMH/NHGRI, National Institutes of Health Building 36, Room 3D06 Bethesda, MD 20892, USA

*To whom correspondence should be addressed. Tel: +972 2 6758614; Fax: +972 2 6757308; Email: hanah{at}md.huji.ac.il

Received February 2, 2005. Revised April 21, 2005. Accepted April 21, 2005.

MicroRNAs (miRNAs) are ~22 nt-long non-coding RNA molecules, believed to play important roles in gene regulation. We present a comprehensive analysis of the conservation and clustering patterns of known miRNAs in human. We show that human miRNA gene clustering is significantly higher than expected at random. A total of 37% of the known human miRNA genes analyzed in this study appear in clusters of two or more with pairwise chromosomal distances of at most 3000 nt. Comparison of the miRNA sequences with their homologs in four other organisms reveals a typical conservation pattern, persistent throughout the clusters. Furthermore, we show enrichment in the typical conservation patterns and other miRNA-like properties in the vicinity of known miRNA genes, compared with random genomic regions. This may imply that additional, yet unknown, miRNAs reside in these regions, consistent with the current recognition that there are overlooked miRNAs. Indeed, by comparing our predictions with cloning results and with identified miRNA genes in other mammals, we corroborate the predictions of 18 additional human miRNA genes in the vicinity of the previously known ones. Our study raises the proportion of clustered human miRNAs that are <3000 nt apart to 42%. This suggests that the clustering of miRNA genes is higher than currently acknowledged, alluding to its evolutionary and functional implications.


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