Clustering and conservation patterns of human microRNAs

Yael Altuvia, Pablo Landgraf, Gila Lithwick, Naama Elefant, Sébastien Pfeffer, Alexei Aravin, Michael J. Brownstein, Thomas Tuschl, Hanah Margalit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

668 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)2697-2706
Number of pages10
JournalNucleic Acids Research
Volume33
Issue number8
DOIs
StatePublished - 1 Jan 2005

Bibliographical note

Funding Information:
We thank M. Zavolan, R. Sheridan and C. Sander for contributing to identification of miRNAs in the cloning data. M. Chien, J.J. Russo and J. Ju from Columbia Genome Center are thanked for small RNA library sequencing, and R. Hershberg, E. Akiva and Y. Seldin are thanked for their useful comments. This study was supported by grants from the US–Israel Bi-national Science Foundation (H.M. and T.T.), and by a grant from The Israeli Cancer Research Foundation (H.M.). S.P. is supported by the Lehman Brothers Foundation Fellowship through the Leukemia & Lymphoma Society, P.L. is supported by the Dr Mildred Scheel Stiftung für Krebsforschung of the Deutsche Krebshilfe (German Cancer Aid). Funding to pay the Open Access publication charges for this article was provided by The US-Israel Bi-National Science Foundation.

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