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RETRACTED ARTICLE: Hes1 is a target of microRNA-23 during retinoic-acid-induced neuronal differentiation of NT2 cells

This article was retracted on 06 November 2003

A Retraction to this article was published on 06 November 2003

Abstract

MicroRNAs (miRNAs) are phylogenetically widespread small RNAs of 18–25 nucleotides in length, and are found in animals and plants. These small RNAs can regulate gene expression at a translational level through interactions with their target messenger RNAs, and they have a role in the development of Caenorhabditis elegans and plants. Although more than two hundred miRNAs have been found in mammals, their mRNA targets remain to be identified. Here, we demonstrate that the expression of Hes1, basic helix–loop–helix transcriptional repressor, is regulated by miRNA-23 (miR-23) in NT2 cells. miR-23 is almost complementary to part of the coding region, just upstream of the termination codon, of Hes1 mRNA. Reduction in the level of miR-23 by small interfering RNAs resulted in the accumulation of Hes1, and hindered the retinoic-acid-induced neuronal differentiation of NT2 cells. Thus, our results indicate that miR-23 regulates the expression of Hes1 at the post-transcriptional level, and participates in retinoic-acid-induced neuronal differentiation of NT2 cells.

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Figure 1: Expression of Hes1 and miR-23.
Figure 2: Effects of synthetic miR-23 and siRNA–miR-23 targeted to a loop region of the precursor to miR-23 on expression of the HES1 gene.
Figure 3: Target specificity of miR-23 as determined with plasmids that encode a gene for luciferase fused to the sequence of the target site of miR-23 in HES1 mRNA.
Figure 4: The role of miR-23 during the retinoic-acid-induced neuronal differentiation of NT2 cells a, Effects of siRNA–miR-23 on retinoic-acid-induced neuronal differentiation.

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Acknowledgements

The authors thank L. Nelson for critical reading of the manuscript. This research was supported by grants from the Ministry of Economy, Trade and Industry (METI) of Japan, and by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Culture (MEXT) of Japan.

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Correspondence to Hiroaki Kawasaki or Kazunari Taira.

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Additional information

In this article, the messenger RNA that is identified to be a target of microRNA-23 (miR-23) is from the gene termed human ‘homolog of ES1’ (HES1), accession number Y07572, and not from the gene encoding the transcriptional repressor ‘Hairy enhancer of split’ HES1 (accession number NM_00524) as stated in our paper. We incorrectly identified the gene because of the confusing nomenclature. The function of HES1 Y07572 is unknown but the encoded protein shares homology with a protein involved in isoprenoid biosynthesis. Our experiments in NT2 cells had revealed that the protein levels of the repressor Hes1 were diminished by miR-23. Although we have unpublished data that suggest the possibility that miR-23 might also interact with Hes1 repressor mRNA, the explanation for the finding that the level of repressor Hes1 protein decreases in response to miR-23 remains undefined with respect to mechanism and specificity. Given the interpretational difficulties resulting from our error, we respectfully retract the present paper. Further studies aimed at clarifying the physiological role of miR-23 will be submitted to a peer-reviewed journal subject to the outcome of our ongoing research.

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Kawasaki, H., Taira, K. RETRACTED ARTICLE: Hes1 is a target of microRNA-23 during retinoic-acid-induced neuronal differentiation of NT2 cells. Nature 423, 838–842 (2003). https://doi.org/10.1038/nature01730

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