Molecular architecture of a miRNA-regulated 3' UTR.

Molecular architecture of a miRNA-regulated 3' UTR. Research Abstract Details 

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Molecular architecture of a miRNA-regulated 3' UTR. Abstract Text:

Animal genomes contain hundreds of microRNAs (miRNAs), small regulatory RNAs that control gene expression by binding to complementary sites in target mRNAs. Some rules that govern miRNA/target interaction have been elucidated but their general applicability awaits further experimentation on a case-by-case basis. We use here an assay system in transgenic nematodes to analyze the interaction of the Caenorhabditis elegans lsy-6 miRNA with 3' UTR sequences. In contrast to many previously described assay systems used to analyze miRNA/target interactions, our assay system operates within the cellular context in which lsy-6 normally functions, a single neuron in the nervous system of C. elegans. Through extensive mutational analysis, we define features in the known and experimentally validated target of lsy-6, the 3' UTR of the cog-1 homeobox gene, that are required for a functional miRNA/target interaction. We describe that both in the context of the cog-1 3' UTR and in the context of heterologous 3' UTRs, one or more seed matches are not a reliable predictor for a functional miRNA/target interaction. We rather find that two nonsequence specific contextual features beyond miRNA target sites are critical determinants of miRNA-mediated 3' UTR regulation. The contextual features reside 3' of lsy-6 binding sites in the 3' UTR and act in a combinatorial manner; mutation of each results in limited defects in 3' UTR regulation, but a combinatorial deletion results in complete loss of 3' UTR regulation. Together with two lsy-6 sites, these two contextual features are capable of imparting regulation on a heterologous 3' UTR. Moreover, the contextual features need to be present in a specific configuration relative to miRNA binding sites and could either represent protein binding sites or provide an appropriate structural context. We conclude that a given target site resides in a 3' UTR context that evolved beyond target site complementarity to support regulation by a specific miRNA. The large number of 3' UTRs that we analyzed in this study will also be useful to computational biologists in designing the next generation of miRNA/target prediction algorithms.

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Molecular architecture of a miRNA-regulated 3' UTR. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: RNA (New York, N.Y.)

VOLUME: 14

Page Numbers: 1297-317

Journal Abbreviation: RNA

ISSN: 1469-9001

DAY: 7

MONTH: 05

YEAR: 2008

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LANGUAGE: eng

NlmUniqueID: 9509184

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Grant and Affiliation Information for Molecular architecture of a miRNA-regulated 3' UTR.

AFFILIATION: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University Medical Center, New York, New York 10032, USA.

Country: United States

AGENCY: United States Howard Hugh

GRANT: R01 NS050266-01

ACRONYM: NS

MEDLINETA: RNA

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