Redox Balance-DDR-miRNA Triangle: Relevance in Genome Stability and Stress Responses in Plants

Abstract

Plants are continuously faced with complex environmental conditions which can affect the oxidative metabolism and photosynthetic efficiency, thus leading to the over-production of reactive oxygen species (ROS). Over a certain threshold, ROS can damage DNA. DNA damage, unless repaired, can affect genome stability, thus interfering with cell survival and severely reducing crop productivity. A complex network of pathways involved in DNA damage response (DDR) needs to be activated in order to maintain genome integrity. The expression of specific genes belonging to these pathways can be used as indicators of oxidative DNA damage and effective DNA repair in plants subjected to stress conditions. Managing ROS levels by modulating their production and scavenging systems shifts the role of these compounds from toxic molecules to key messengers involved in plant tolerance acquisition. Oxidative and anti-oxidative signals normally move among the different cell compartments, including the nucleus, cytosol, and organelles. Nuclei are dynamically equipped with different redox systems, such as glutathione (GSH), thiol reductases, and redox regulated transcription factors (TFs). The nuclear redox network participates in the regulation of the DNA metabolism, in terms of transcriptional events, replication, and repair mechanisms. This mainly occurs through redox-dependent regulatory mechanisms comprising redox buffering and post-translational modifications, such as the thiol-disulphide switch, glutathionylation, and S-nitrosylation. The regulatory role of microRNAs (miRNAs) is also emerging for the maintenance of genome stability and the modulation of antioxidative machinery under adverse environmental conditions. In fact, redox systems and DDR pathways can be controlled at a post-transcriptional level by miRNAs. This review reports on the interconnections between the DDR pathways and redox balancing systems. It presents a new dynamic picture by taking into account the shared regulatory mechanism mediated by miRNAs in plant defense responses to stress.

Keywords: DDR; cell cycle checkpoints; miRNA; redox balance; redox-sensitive TFs.

FIGURE 1

Cellular redox balance-DDR-miRNA triangle. An increase in ROS production generally occurs early under different stress conditions. ROS and redox signals move through different cell compartments. In the nucleus, ROS accumulation can cause DNA damage thus inducing cell cycle arrest. The DDR specifically aims to help plants cope with the negative effects of genotoxic stress. Alterations in antioxidant and oxidant balance in the nucleus are required to promote cell cycle progression in the right redox environment. In this context, ROS and redox signals are involved in the regulation of gene expression at transcriptional and post-transcriptional levels. The picture shows some examples of the redox dependent transcriptional mechanisms involving some redox-sensitive TFs, such as SRG1, PAN, and HSFA8, in gene expression regulation. At the post-transcriptional level, the figure also shows the modulation of redox- and DDR-related target mRNAs by miRNAs. AOx, antioxidants; DCL1, DICER-like1; DDR, DNA damage responses; HSFA8, heat shock factor A8; miRNA, microRNA; Ox, oxidants; PAN, PERIANTHIA; RNS, reactive nitrogen species; ROS, reactive oxygen species; SRG1, SNO-regulated gene 1.