Biogenesis of Developmental Master Regulatory 27nt-RNAs in Stylonychia—Can Coding RNA Turn into Non-Coding?
Clinical Molecular Genetics and Epigenetics, Faculty of Health, Centre for Biomedical Education & Research (ZBAF), Helios University Hospital Wuppertal (Zentrum für Forschung in der Klinischen Medizin—ZFKM), Witten/Herdecke University, Alfred-Herrhausen-Str. 50, 58448 Witten, Germany
Author to whom correspondence should be addressed.
Genes 2019, 10(11), 940; https://doi.org/10.3390/genes10110940
Received: 18 September 2019 / Revised: 11 November 2019 / Accepted: 13 November 2019 / Published: 18 November 2019
(This article belongs to the Special Issue Ciliate Genetics and Epigenetics)
In the ciliate Stylonychia, somatic macronuclei differentiate from germline micronuclei during sexual reproduction, accompanied by developmental sequence reduction. Concomitantly, over 95% of micronuclear sequences adopt a heterochromatin structure characterized by the histone variant H3.4 and H3K27me3. RNAi-related genes and histone variants dominate the list of developmentally expressed genes. Simultaneously, 27nt-ncRNAs that match sequences retained in new macronuclei are synthesized and bound by PIWI1. Recently, we proposed a mechanistic model for ‘RNA-induced DNA replication interference’ (RIRI): during polytene chromosome formation PIWI1/27nt-RNA-complexes target macronucleus-destined sequences (MDS) by base-pairing and temporarily cause locally stalled replication. At polytene chromosomal segments with ongoing replication, H3.4K27me3-nucleosomes become selectively deposited, thus dictating the prospective heterochromatin structure of these areas. Consequently, these micronucleus-specific sequences become degraded, whereas 27nt-RNA-covered sites remain protected. However, the biogenesis of the 27nt-RNAs remains unclear. It was proposed earlier that in stichotrichous ciliates 27nt-RNA precursors could derive from telomere-primed bidirectional transcription of nanochromosomes and subsequent Dicer-like (DCL) activity. As a minimalistic explanation, we propose here that the 27nt-RNA precursor could rather be mRNA or pre-mRNA and that the transition of coding RNA from parental macronuclei to non-coding RNAs, which act in premature developing macronuclei, could involve RNA-dependent RNA polymerase (RDRP) activity creating dsRNA intermediates prior to a DCL-dependent pathway. Interestingly, by such mechanism the partition of a parental somatic genome and possibly also the specific nanochromosome copy numbers could be vertically transmitted to the differentiating nuclei of the offspring.