Change: Piwi-interacting RNA

created on Nov. 30, 2012, 11:37 p.m. by Hevok & updated on Dec. 1, 2012, 12:46 a.m. by Hevok

RNA interference can be heritable, which means that it can have transgenerational effects [Burton et al. 2011]. Responsible for this appears to be piwi-interacting RNAs (piRNAs) [Brennecke et al. 2008; Grentzinger et al. 2012]. piRNAs are slightly longer than microRNAs and associated with RNA-protein complexes, mediated by the binding to Piwi proteins. piRNAs represent a much bigger class of non-coding RNA than microRNAs. piRNAs are associated with gene silencing, most especially at repeat elements like transposons [Aravin et al. 2008]. piRNAs are important in the germline, where they can aid in establishing other epigenetic patterns like DNA methylation and histone modifications.

piRNA cis-regulate DNA-methylation. A methylation determining region produces a specialized form of RNA (pit-RNA) that is essential for methylation in cis [Park et al. 2012]. Heritable piRNA appears to direct methylation occurring in mammalian germ cells. Mice lacking certain piRNAs fail to re-methylate properly after the loss of methylation during fertilization [Aravin et al. 2008; Aravin & Bourc'his, 2008; Ashe et al. 2012]. piRNAs cluster at L1 promoter, indicating that they are involved in establishment of DNA methylation.

piRNAs are responsible for inheritance of histone marks in C. elegans, which lack DNA methylation [Burton et al. 2011].

In C. elegans longevity conferred through deficiencies in H3K4me3 chromatin modifiers ASH-2, WDR5 or SET-2 is inherited transgenerational, which requires the presence of a functioning germline in the descendants [Greer et al. 201].

The expression of piRNA is downregulated during aging in C. elegans [Kato et al. 2011].


Burton NO, Burkhart KB, Kennedy S. Nuclear RNAi maintains heritable gene silencing in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. (2011).

Brennecke J, Malone CD, Aravin AA, Sachidanandam R, Stark A, Hannon GJ. An epigenetic role for maternally inherited piRNAs in transposon silencing. Science. 322(5906), 1387–1392 (2008).

Grentzinger T, Armenise C, Brun C, et al. piRNA-mediated transgenerational inheritance of an acquired trait. Genome Res. (2012).

Aravin AA, Sachidanandam R, Bourc'his D, et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell. 31(6), 785–799 (2008).

Park YJ, Herman H, Gao Y, et al. Sequences sufficient for programming imprinted germline DNA methylation defined. PLoS ONE. 7(3), e33024 (2012).

Aravin AA, Bourc'his D. Small RNA guides for de novo DNA methylation in mammalian germ cells. Genes Dev. 22(8), 970–975 (2008).

Ashe A, Sapetschnig A, Weick E-M, et al. piRNAs Can Trigger a Multigenerational Epigenetic Memory in the Germline of C.elegans. Cell. 1–12 (2012).

Burton NO, Burkhart KB, Kennedy S. Nuclear RNAi maintains heritable gene silencing in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. (2011).

Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A (2011) Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature 479: 365-71.

Kato M, Chen X, Inukai S, Zhao H, Slack FJ. Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans. RNA. 17(10), 1804–1820 (2011).


Parent: Aging

Comment: Added further paragraphs.

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