A pathogenic long non-coding RNA redesigns the epigenetic landscape of the infected cells by subverting host Histone Deacetylase 6 activity

[EN] Viroids - ancient plant-pathogenic long noncoding RNAs - have developed a singular evolutionary strategy based on reprogramming specific phases of host-metabolism to ensure that their infection cycle can be completed in infected cells. However, the molecular aspects governing this transregulatory phenomenon remain elusive. Here, we use immunoprecipitation assays and bisulfite sequencing of rDNA to shown that, in infected cucumber and Nicotiana benthamina plants, Hop stunt viroid (HSVd) recruits and functionally subverts Histone Deacetylase 6 (HDA6) to promote host-epigenetic alterations that trigger the transcriptional alterations observed during viroid pathogenesis. This notion is supported by the demonstration that, during infection, the HSVd-HDA6 complex occurs invivo and that endogenous HDA6 expression is increased in HSVd-infected cells. Moreover, transient overexpression of recombinant HDA6 reverts the hypomethylation status of rDNA observed in HSVd-infected plants and reduces viroid accumulation. We hypothesize that the host-transcriptional alterations induced as a consequence of viroid-mediated HDA6 recruitment favor spurious recognition of HSVd-RNA as an RNA Pol II template, thereby improving viroid replication. Our results constitute the first description of a physical and functional interaction between a pathogenic RNA and a component of the host RNA silencing mechanism, providing novel evidence of the potential of these pathogenic lncRNAs to physically redesign the host-cell environment and reprogram their regulatory mechanisms.The authors thank Dr M. Fares for the contribution to the statistical analysis of the data and Dr G. Martinez for the critical reading of this manuscript. This work was supported by grants AGL2013-47886-R and BIO2014-61826-EXP (GG) and BIO2014-54862-R (VP) from the Spanish Granting Agency (Direccion General Investigacion Cientifica).Castellano Perez, M.; Pallás Benet, V.; Gomez, GG. (2016). A pathogenic long non-coding RNA redesigns the epigenetic landscape of the infected cells by subverting host Histone Deacetylase 6 activity. New Phytologist. 211(4):1311-1322. doi:10.1111/nph.1400113111322211