The long non-coding RNALINDArestrains cellular collapse following DNA damage inArabidopsis thaliana

Abstract

SUMMARYThe genomic integrity of every organism is endangered by various intrinsic and extrinsic stresses. To maintain the genomic integrity, a sophisticated DNA damage response (DDR) network is activated rapidly after DNA damage. Notably, the fundamental DDR mechanisms are conserved in eukaryotes. However, knowledge about many regulatory aspects of the plant DDR is still limited. Important, yet little understood, regulatory factors of the DDR are the long non-coding RNAs (lncRNAs). In humans, 13 lncRNAs functioning in DDR have been characterized to date, whereas no such lncRNAs have been characterized in plants yet. By meta-analysis, we identified thelong intergenicnon-coding RNA induced by DNAdamage(LINDA) that responds strongly to various DNA double-strand break-inducing treatments, but not to replication stress induced by mitomycin C. After DNA damage,LINDAis rapidly induced in an ATM- and SOG1-dependent manner. Intriguingly, the transcriptional response ofLINDAto DNA damage is similar to that of its flanking hypothetical protein-encoding gene. Phylogenetic analysis of putative Brassicales and MalvalesLINDAhomologs indicates thatLINDAlncRNAs originate from duplication of a flanking small protein-encoding gene followed by pseudogenization. We demonstrate thatLINDAis not only needed for the regulation of this flanking gene, but also for fine-tuning of the DDR after the occurrence of DNA double-strand breaks. Moreover, Δlindamutant root stem cells are unable to recover from DNA damage, most likely due to hyper-induced cell death.SIGNIFICANT STATEMENTWe unraveled the functional relevance of the first lncRNA within the DNA damage response network ofArabidopsis thaliana.This lncRNA, termedLINDA, is an important part of the DNA damage response network, as it is needed for accurate regulation of cell death and cell cycle progression.