Small RNAs in epigenetic inheritance: from mechanisms to trait transmission

FEBS Lett. 2021 Dec;595(24):2953-2977. doi: 10.1002/1873-3468.14210. Epub 2021 Oct 29.


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.

Keywords: RNA interference; epigenetics; gene regulation; gene silencing; miRNAs; piRNAs; small RNAs; transgenerational epigenetic inheritance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Epigenesis, Genetic*
  • Humans
  • Inheritance Patterns / genetics*
  • Models, Animal
  • Quantitative Trait, Heritable*
  • RNA / metabolism*
  • RNA Interference


  • RNA