Work

Dispatched Homolog 2 is targeted by miR-214 through a combination of three weak microRNA recognition sites

Year: 2008

Type: article

Abstract: MicroRNAs (miRNAs) regulate gene expression by inhibiting translation of target mRNAs through pairing with miRNA recognition elements (MREs), usually in 3' UTRs. Because pairing is imperfect, identification of bona fide mRNA targets presents a challenge. Most target recognition algorithms strongly emphasize pairing between nucleotides 2-8 of the miRNA (the 'seed' sequence) and the mRNA but adjacent sequences and the local context of the 3' UTR also affect targeting. Here, we show that dispatched 2 is a target of miR-214. In zebrafish, dispatched 2 is expressed in the telencephalon and ventral hindbrain and is essential for normal zebrafish development. Regulation of dispatched 2 by miR-214 is via pairing with three, noncanonical, weak MREs. By comparing the repression capacity of GFP reporters containing different dispatched 2 sequences, we found that a combination of weak sites, which lack canonical seed pairing, can effectively target an mRNA for silencing. This finding underscores the challenge that prediction algorithms face and emphasizes the need to experimentally validate predicted MREs.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkn388

Authors: N. Li, A. S. Flynt, H. R. Kim, L. Solnica-Krezel, J. G. Patton

Institutions: Vanderbilt University, University of Sheffield

Language: English

Topic: MicroRNA in disease regulation

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,992

Funders: National Institutes of Health, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development