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. 2007 Jan 30;1(1-2):29–33. doi: 10.1007/s11568-006-9000-3

Searching for potential microRNA-binding site mutations amongst known disease-associated 3′ UTR variants

Nadia Chuzhanova 1, David N Cooper 1, Claude Férec 2,3,4,5, Jian-Min Chen 2,3,4,✉
PMCID: PMC2276887  PMID: 18923926

Abstract

The 3′ untranslated regions (3′ UTRs) of human protein-coding genes play a pivotal role in the regulation of mRNA 3′ end formation, stability/degradation, nuclear export, subcellular localisation and translation, and hence are particularly rich in cis-acting regulatory elements. One recent addition to the already large repertoire of known cis-acting regulatory elements are the microRNA (miRNA) target sites that are present in the 3′ UTRs of many human genes. miRNAs post-transcriptionally down-regulate gene expression by binding to complementary sequences on their cognate target mRNAs, thereby inducing either mRNA degradation or translational repression. To date, only one disease-associated 3′ UTR variant (in the SLITRK1 gene) has been reported to occur within a bona fide miRNA binding site. By means of sequence complementarity, we have performed the first systematic search for potential miRNA-target site mutations within a set of 79 known disease-associated 3′ UTR variants. Since no variants were found that either disrupted or created binding sites for known human miRNAs, we surmise that miRNA-target site mutations are not likely to represent a frequent cause of human genetic disease.

Keywords: Cis-acting regulatory elements, Human inherited disease, MicroRNA, MiRNA target site mutation, 3′ Untranslated region, 3′ UTR

Acknowledgements

This work was performed during early 2006 while JMC was a visiting Professor of Genetics supported by the Ministère de la Jeunesse, de l’Éducation Nationale et de la Recherche, France. This work was supported by the INSERM (Institut National de la SantÉ et de la Recherche MÉdicale), France.

Abbreviations

LAS

Left arm of the ‹spacer’ sequence between the upstream core polyadenylation signal and the pre-mRNA cleavage site

miRNA

MicroRNA

UCPAS

Upstream core polyadenylation signal

USS

Upstream sequence between the translational termination codon and the UCPAS

3′ UTR

3′ Untranslated region

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