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Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions

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Abstract

We use Caenorhabditis elegans to test proposed general rules for microRNA (miRNA)-target interactions. We show that G·U base pairing is tolerated in the 'seed' region of the lsy-6 miRNA interaction with its in vivo target cog-1, and that 6- to 8-base-pair perfect seed pairing is not a generally reliable predictor for an interaction of lsy-6 with a 3′ untranslated region (UTR). Rather, lsy-6 can functionally interact with its target site only in specific 3′ UTR contexts. Our findings illustrate the difficulty of establishing generalizable rules of miRNA-target interactions.

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Figure 1: Responsiveness of various 3′ UTRs to lsy-6.
Figure 2: lsy-6 responsiveness of G·U-wobbled 3′ UTRs and predicted lsy-6 target 3′ UTRs, represented as in Figure 1.

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Acknowledgements

We thank Q. Chen for expert technical assistance in generating transgenic strains, N. Rajewsky for stimulating discussions, I. Rigoutsos for suggestions about target predictions and R. Mann, F. Slack, I. Greenwald, P. Sengupta, I. Rigoutsos and N. Rajewsky for comments on the manuscript. This work was funded, in part, by US National Institutes of Health grants 1R03HD050334-01 and 5R01NS050266-02, a predoctoral US National Institutes of Health fellowship to D.D. and the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, Howard Hughes Medical Institute, 701 W. 168th Street, New York, 10032, New York, USA

    Dominic Didiano & Oliver Hobert

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  1. Dominic Didiano
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  2. Oliver Hobert
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Correspondence to Oliver Hobert.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

lsy-6 responsiveness of predicted lsy-6 target 3′ UTRs. (PDF 115 kb)

Supplementary Fig. 2

Conservation of seed matches to lsy-6 from C. elegans to C. briggsae. (PDF 114 kb)

Supplementary Table 1

Primers and transgenic arrays. (PDF 59 kb)

Supplementary Methods (PDF 78 kb)

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Didiano, D., Hobert, O. Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions. Nat Struct Mol Biol 13, 849–851 (2006). https://doi.org/10.1038/nsmb1138

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