Advertisement
Review

Epigenetic Regulation by Heritable RNA

  • Reinhard Liebers,

    Affiliation: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany

    X
  • Minoo Rassoulzadegan,

    Affiliations: University of Nice Sophia Antipolis, Nice, France, Inserm UMR1091, CNRS UMR7277, Nice, France

    X
  • Frank Lyko mail

    f.lyko@dkfz.de

    Affiliation: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany

    X
  • Published: April 17, 2014
  • DOI: 10.1371/journal.pgen.1004296

Reader Comments (1)

Post a new comment on this article

More evidence for RNA effects on epigenetic inheritance

Posted by jnadeau on 28 Apr 2014 at 21:35 GMT

The Heaney paper shows that paternal heterozygosity for a Kit ligand deletion protects wild-type sons from testicular cancer. This story involves a different trait than the Kit receptor work, - germ cell cancer versus pigmentation. But it nicely implicated Kit ligand - receptor signaling in epigenetic effects and transgenerational inheritance.

Two papers on Dnd1 and Apobec1 are also relevant. Dnd1 is related by sequence to Apobec1 complementation factor (A1cf), which is the RNA binding factor for Apobec1 cytidine deaminase in RNA editing. Dnd1 also controls access of certain miRNAs to their mRNA targets (Kede et al Cell 2007). Lam et al 2006 showed that the Dnd1*Ter mutation controls epigenetically inherited risk for testicular cancer. In parallel, Apobec1 clearly affects transgenerational risk for testicular cancer, and its only known function is RNA editing. So both Dnd1 and Apobec1 are involved in a relevant phenotype, a mouse model for an important cancer in humans, and provide compelling evidence implicating important aspects of RNA biology in epigenetic inheritance.

Heaney, J.D., M.-Y.J. Lam, and J.H. Nadeau (2008) Loss of the transmembrane but not the soluble Kit ligand isoform increases testicular germ cell tumor susceptibility in mice. Cancer Res. 68: 5193-5197.

Lam, M.-Y.J., J. Heaney, K.K. Youngren, J.H. Kawasoe, and J.H. Nadeau (2007) Transgenerational epistasis between Dnd1*Ter and other modifier genes controls susceptibility to testicular germ cell tumors. Hum. Mol. Genet. 16:2233-2240.

Nelson, V.R., J.D. Heaney, P.J. Tesar, N.O. Davidson, and J.H. Nadeau (2012) Transgenerational genetic effects of Apobec1 cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability. Proc. Natl. Acad. Sci. USA 109:E2766-73.

No competing interests declared.