27nt-RNAs guide histone variant deposition via 'RNA-induced DNA replication interference' and thus transmit parental genome partitioning in Stylonychia

Epigenetics Chromatin. 2018 Jun 12;11(1):31. doi: 10.1186/s13072-018-0201-5.


Background: During sexual reproduction in the unicellular ciliate Stylonychia somatic macronuclei differentiate from germline micronuclei. Thereby, programmed sequence reduction takes place, leading to the elimination of > 95% of germline sequences, which priorly adopt heterochromatin structure via H3K27me3. Simultaneously, 27nt-ncRNAs become synthesized from parental transcripts and are bound by the Argonaute protein PIWI1.

Results: These 27nt-ncRNAs cover sequences destined to the developing macronucleus and are thought to protect them from degradation. We provide evidence and propose that RNA/DNA base-pairing guides PIWI1/27nt-RNA complexes to complementary macronucleus-destined DNA target sequences, hence transiently causing locally stalled replication during polytene chromosome formation. This spatiotemporal delay enables the selective deposition of temporarily available histone H3.4K27me3 nucleosomes at all other sequences being continuously replicated, thus dictating their prospective heterochromatin structure before becoming developmentally eliminated. Concomitantly, 27nt-RNA-covered sites remain protected.

Conclusions: We introduce the concept of 'RNA-induced DNA replication interference' and explain how the parental functional genome partition could become transmitted to the progeny.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / metabolism
  • Ciliophora / genetics
  • Ciliophora / physiology*
  • DNA Replication*
  • Genetic Variation
  • Genome, Protozoan
  • Histones / genetics*
  • Micronucleus, Germline / genetics
  • RNA, Guide, Kinetoplastida / genetics*
  • RNA, Protozoan / genetics


  • Argonaute Proteins
  • Histones
  • RNA, Guide
  • RNA, Protozoan