Guest list or black list: heritable small RNAs as immunogenic memories

Trends Cell Biol. 2014 Apr;24(4):212-20. doi: 10.1016/j.tcb.2013.10.003. Epub 2013 Nov 11.


Small RNA-mediated gene silencing plays a pivotal role in genome immunity by recognizing and eliminating viruses and transposons that may otherwise colonize the genome. However, individual genomic parasites are highly diverse and employ multiple immune-evasion techniques, making this silencing challenging. Here I review a new theory proposing that the integrity of the germline is maintained by transgenerationally transmitted RNA 'memories' that record ancestral gene expression patterns and delineate 'self' from 'foreign' sequences. To maintain such recollection, two tactics are employed in parallel: 'black listing' of invading nucleic acids and 'guest listing' of endogenous genes. Studies in several organisms have shown that this memorization is used by the next generation of small RNAs to act as 'inherited vaccines' that attack invading elements or as 'inherited licenses' that permit the transcription of autogenous sequences.

Keywords: inherited immunity; inherited vaccines; self versus non-self; small RNA; transgenerational inheritance.

Publication types

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

MeSH terms

  • Animals
  • Germ Cells / immunology
  • Humans
  • Immunogenetic Phenomena*
  • Immunologic Memory*
  • RNA Interference / immunology*
  • RNA, Small Interfering / immunology*
  • RNA, Small Interfering / metabolism


  • RNA, Small Interfering