Journal article

The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and lgf1r

Andrew Keniry, David Oxley, Paul Monnier, Michael Kyba, Luisa Dandolo, Guillaume Smits, Wolf Reik

NATURE CELL BIOLOGY | NATURE PUBLISHING GROUP | Published : 2012

Abstract

The H19 large intergenic non-coding RNA (lincRNA) is one of the most highly abundant and conserved transcripts in mammalian development, being expressed in both embryonic and extra-embryonic cell lineages, yet its physiological function is unknown. Here we show that miR-675, a microRNA (miRNA) embedded in H19's first exon, is expressed exclusively in the placenta from the gestational time point when placental growth normally ceases, and placentas that lack H19 continue to grow. Overexpression of miR-675 in a range of embryonic and extra-embryonic cell lines results in their reduced proliferation; targets of the miRNA are upregulated in the H19 null placenta, including the growth-promoting in..

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University of Melbourne Researchers

Grants

Awarded by NIH/NHLBI


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by Biotechnology and Biological Sciences Research Council


Awarded by Medical Research Council


Awarded by BBSRC


Awarded by MRC


Funding Acknowledgements

We thank D. L. Kontoyiannis (Alexander Fleming Biomedical Sciences Research Center, Greece) for supplying HuR<SUP>-/-</SUP> MEF cells. We also thank H. Jammes and A. Gabory for assisting with collection of the H19<SUP>Delta 3</SUP> phenotypic data, J. Webster for preparing samples for mass spectrometry and W. Dean for tissue collections. The authors would also like to thank K. Tabbada, A. Segonds-Pichon and S. Andrews for RNA sequencing, statistical and bioinformatic assistance, respectively. We thank M. lacovino for creating the A2lox-cre ES cell line. We would also like to thank T. Hore, C. Krueger and J. Houseley for critical reading of the manuscript and all members of the laboratories of W. Reik, M. Hemberger, E. Vigorito and). Houseley for helpful discussions. This work was supported by BBSRC, the Wellcome Trust, MRC, EU NoE EpiGeneSys, EU BLUEPRINT, NIH/NHLBI (U01HL100407) and the Cambridge Commonwealth Trust.