Round and round it goes: a cyclic nucleotide modulates stress responses in plants

To survive, living organisms must perceive environmental fluctuations and develop the proper responses. For this purpose, all biological systems utilize multiple signaling molecules that translate external signals into specific developmental responses and help them cope with the environmental conditions faced. Among these, cyclic nucleotides comprise a group of evolutionary conserved chemical signals that regulate a vast number of biological processes across the tree of life (Swiezawska et al., 2018). For instance, 3′,5′-cycic adenosine monophosphate (3′5′-cAMP, Figure 1A) has long been recognized as one of the most important signaling molecules in human cells and its role in plants was just recently identified as a modulator of growth, photosynthesis, and biotic and abiotic stress responses (Gehring and Turek, 2017). Interestingly, while 3′5′-cAMP has been exhaustively studied for the past 50 years, little is known about the functions of its positional isomer, 2′3′-cAMP (Figure 1B), even though the latter also participates in a wide range of environmental responses in eukaryotic cells (Van Damme et al., 2014; Jackson, 2016). This knowledge gap hinders our capacity to fully comprehend how living organisms utilize cyclic nucleotides to thrive under different environmental conditions.

Figure 1.

Cyclic nucleotides modulate stress responses in plants. In this issue of Plant Physiology, Chodasiewicz and colleagues (2021) demonstrate that a positional isomer of the cyclic nucleotide 3′5′-cAMP (A), 2′3′-cAMP (B), is a signaling molecule involved in the regulation of specific stress responses in the plant model Arabidopsis thaliana. Adapted from Jackson (2011).

In this issue of Plant Physiology, Chodasiewicz and colleagues (2022) shed some light in this topic by uncovering the role of 2′3′-cAMP in the plant model Arabidopsis (Arabidopsis thaliana). For this purpose, the authors performed metabolomic analysis on liquid-grown Arabidopsis seedlings treated with 1 µM of 2′3′-cAMP. About 15 min after 2′3′-cAMP treatment, the production of 80 primary and specialized metabolites was significantly affected, indicating the accumulation of amino acids, proteogenic dipeptides, and degradation products of 2′3′-cAMP itself when compared with untreated control plants. This finding is remarkably similar to plants subjected to stressful conditions, such as heat and darkness (Thirumalaikumar et al., 2021), indicating that 2′3′-cAMP may be involved with responses to environmental stress in Arabidopsis.

To gain further insights into the role of this cyclic nucleotide in plants, Chodasiewicz and colleagues (2021) performed transcriptome analysis on Arabidopsis treated with 1 µM 2′3′-cAMP. They observed that 2′3′-cAMP lead to a large transcriptional reprograming in Arabidopsis seedlings, resulting in almost 1,000 differentially expressed genes (DEGs) 30 min after treatment and nearly 3,000 DEGs 6 h after treatment when compared with untreated control plants. Gene ontology analysis indicated that several biological processes related to stress responses are upregulated by 2′3′-cAMP, including “response to salt stress,” “response to wounding,” and “defense response to bacterium.” Further metabolomic analysis confirmed these results, indicating, for example, that 2′3′-cAMP lead to the accumulation of glucosinolates, sulfur-containing specialized metabolites that are related to plant responses to wounding and defense against pests (Campos et al., 2016). Interestingly, other stress responses such as “response to oxidative stress” and “heat stress response” were among the downregulated categories of DEGs followed by 2′3′-cAMP treatment. This finding suggests that 2′3′-cAMP might have an antagonistic function in cell responses to stress, possibly working as a regulator of specific environmental signals in plants.

Given that 2′3′-cAMP is a product of RNA degradation (Jackson, 2016), Chodasiewicz and colleagues (2021) evaluated whether this cyclic nucleotide may be involved with reorganization of processing bodies (PBs), membraneless organelles containing RNA–protein complexes that are involved in the regulation of mRNA decay (Xu and Chua, 2011). For this purpose, they focused on DECAPPING PROTEIN1DCP1, a well-known component of PBs responsible for RNA decapping (Xu and Chua, 2011). The authors used Arabidopsis seedlings expressing DCP1 fused to a green fluorescent marker (GFP-DCP1) and followed GFP-DCP1 movement after 100 µM 2′3′-cAMP treatment using confocal microscopy. This experiment demonstrated that 2′3′-cAMP significantly induces displacement length and PB movement speed when compared with water-treated control samples, confirming that this cyclic nucleotide is involved in the regulation of PB mobility.

The integration between external signal perception and modulation of cellular functions is a fundamental tenet of living organisms. Work by Chodasiewicz and colleagues (2021) uncovers the role of 2′3′-cAMP, a signaling molecule that is involved in the regulation of stress responses in Arabidopsis plants. Even though more work is necessary to fully comprehend how this cyclic nucleotide is involved in plant responses to specific environmental conditions, what downstream signaling responses are mediated by 2′3′-cAMP, and if this molecule is utilized similarly among other plant species, this study provides a starting ground for future research focused on the manipulation of signal transduction pathways to produce stress resistant crops.

Conflict of interest statement. None declared.