Small RNAs in epigenetic inheritance: from mechanisms to trait transmission

Abstract

Inherited information is transmitted to progeny primarily by the genome through the gametes. However, in recent years, epigenetic inheritance has been demonstrated in several organisms, including animals. Although it is clear that certain post-translational histone modifications, DNA methylation, and noncoding RNAs regulate epigenetic inheritance, the molecular mechanisms responsible for epigenetic inheritance are incompletely understood. This review focuses on the role of small RNAs in transmitting epigenetic information across generations in animals. Examples of documented cases of transgenerational epigenetic inheritance are discussed, from the silencing of transgenes to the inheritance of complex traits, such as fertility, stress responses, infections, and behavior. Experimental evidence supporting the idea that small RNAs are epigenetic molecules capable of transmitting traits across generations is highlighted, focusing on the mechanisms by which small RNAs achieve such a function. Just as the role of small RNAs in epigenetic processes is redefining the concept of inheritance, so too our understanding of the molecular pathways and mechanisms that govern epigenetic inheritance in animals is radically changing.

Inheritance and maintenance of small RNA‐mediated epigenetic effects

“…Various examples of inherited acquired traits are controlled by heritable small RNAs (reviewed in Ref. [5]). The transfer of small RNA from parent to offspring requires small RNAs to be packaged in gametes and directly transmitted to the embryo.…”

“…[6] heritable small RNAs (reviewed in Ref. [5]). The capacity of small RNAs to be delivered to the embryo by the gametes and their ability to propagate and maintain the epigenetic responses across generations is an essential aspect of the epigenetic inheritance processes controlled by small RNAs.…”

“…Small noncoding RNAs have been identified as epigenetic factors, together with histone modifications and DNA methylation. [ 3–5 ] Pioneering studies of the RNA interference (RNAi) phenomenon in the nematode Caenorhabditis elegans first revealed the potential role of small RNAs in epigenetic inheritance. Worms injected with double stranded RNAs (dsRNAs) complementary to an mRNA target displayed the silencing of the gene locus even in offspring not exposed to dsRNAs [ 6,7 ] (see Box 1).…”

“…In addition to heritable RNAi responses, the inheritance of complex traits, such as fertility, immune responses to pathogen infection, different types of stresses, and learned behavior, are controlled by heritable small RNAs (reviewed in Ref. [5]). The capacity of small RNAs to be delivered to the embryo by the gametes and their ability to propagate and maintain the epigenetic responses across generations is an essential aspect of the epigenetic inheritance processes controlled by small RNAs.…”

“…Mechanisms regulating the soma to germline transfer of small RNAs also participate in the inheritance of somatic responses to different stimuli across generations. [ 5,9 ]…”