Cinderella of chemical biology | Max Planck Society

Small, so far largely unnoticed molecules have regulatory functions in reducing stress

Living organisms produce many small molecular compounds. Although human
now they know that they play an important role in living things are their functions
mostly unknown. In order to fill this gap in knowledge, and because small molecules via
protein binding, a group led by Aleksandra Skirycz at Max Planck
The Institute of Plant Molecular Physiology has developed a new strategy for identifying such
complexes of protein molecules. An important group of small molecules below this
a novel strategy that can be identified are 2′,3′-cAMP nucleotides, prodn
RNA degradation and apparently play an important role in regulation
play stress reactions.

In unfavorable conditions, living beings – regardless of whether they are bacteria, plants, animals or humans – react with stress. Chronic stress in humans leads to negative effects on the metabolism, immune and cardiovascular systems and impairs sleep regulation, learning, memory and attention processes. Plants are considered stressed when there is impairment of plant growth or reproductive ability. They are often stressed by, among other things, drought, heat, frost, salty soil or lack of nutrients. Reason enough to investigate more closely which processes take place inside living beings under stress and which processes are decisive. In the future, this knowledge could help plants better cope with stress, which would positively affect crop quality and yields. It has already been shown in the past that stress leads to the accumulation of 2′,3′-cyclic nucleotides (small RNA molecules). Until now, this fact has not been paid much attention, because these molecules are an intermediate product of RNA degradation, to which no function could previously be attributed.

Monika Chodasiewicz, until recently a postdoctoral fellow at the Max Planck Institute for Molecular Plant Physiology in Potsdam-Golm in the working group of Aleksandra Skirycz, now a professor at King Abdullah University in Saudi Arabia, explains: “Since our 2018 research results already suggested that 2′, 3′-cAMP may have a regulatory role in the formation of stress granules, we were sure there had to be more than that.”

Stress granules are dense clusters of proteins and RNA in the cytosol that form when a cell is under stress. Since then, the two scientists have suspected that 2′,3′-cAMP may serve as a signaling molecule to initiate molecular changes in response to stress. In fact, in this paper, using an omics approach combined with cell biology, they were able to show that the addition of 2′,3′-cAMP triggers a cellular response that mimics the stress response. Application of 2′,3′-cAMP led to changes at the level of the transcriptome (RNA molecule), proteome (protein) and metabolome (composition of ingredients) in their test plants. The observed changes correspond to reactions that occur under stress. In addition, 2′,3′-cAMP affects the so-called process bodies, which are microscopic, confined structures in the cell, consisting of enzymes that play an important role in mRNA degradation.

Aleksandra Skirycz Skiycz, a professor at the Boyce Thompson Institute and Cornell University in the US, explains: “Our work is another important indication that many of the most important small molecule regulators are chemically simple and evolutionarily ancient compounds.” Since they look rather inconspicuous, they might as well be called the Cinderellas of chemical biology.” Small molecules offer unique opportunities for drug and agrochemical development based on their signaling and regulatory functions. Therefore, the research results so far could lead to innovations in the field of cyclic nucleotides aimed at changing and ideally improving plant health and plant responses to environmental stimuli. “Our discoveries open up a new dimension of research and offer new possibilities for investigating previously undiscovered signaling pathways,” says Monika Chodasiewicz, commenting on the results of the working group’s research.



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