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Comparative and Functional Genomics
Volume 2011 (2011), Article ID 910769, 9 pages
http://dx.doi.org/10.1155/2011/910769
Research Article

The Influence of 3′UTRs on MicroRNA Function Inferred from Human SNP Data

1Center for Computational Research, New York State Center of Excellence in Bioinformatics and Life Sciences, Departments of Ophthalmology, Biostatistics, and Medicine, State University of New York (SUNY), Buffalo, NY 14260, USA
2SUNY Eye Institute, Syracuse, NY 13202, USA
3Center for Computational Research, New York State Center of Excellence in Bioinformatics and Life Sciences, State University of New York (SUNY), Buffalo, NY 14260, USA

Received 24 May 2011; Revised 14 August 2011; Accepted 22 August 2011

Academic Editor: E. Hovig

Copyright © 2011 Zihua Hu and Andrew E. Bruno. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

MicroRNAs (miRNAs) regulate gene expression posttranscriptionally. Although previous efforts have demonstrated the functional importance of target sites on miRNAs, little is known about the influence of the rest of 3′ untranslated regions (3′UTRs) of target genes on microRNA function. We conducted a genome-wide study and found that the entire 3′UTR sequences could also play important roles on miRNA function in addition to miRNA target sites. This was evidenced by the fact that human single nucleotide polymorphisms (SNPs) on both seed target region and the rest of 3′UTRs of miRNA target genes were under significantly stronger negative selection, when compared to non-miRNA target genes. We also discovered that the flanking nucleotides on both sides of miRNA target sites were subject to moderate strong selection. A local sequence region of ~67 nucleotides with symmetric structure is herein defined. Additionally, from gene expression analysis, we found that SNPs and miRNA target sites on target sequences may interactively affect gene expression.