TRANSLATION AND PROTEIN FOLDING IN RESPONSE TO ENVIRONMENTAL CUES
- Medina Villar, Silvia - Technician
- Muñoz Gutiérrez, Alfonso - Visiting Scientist
- Novo Uzal, Esther - Young Investigator Researcher (YIR)
- Ochoa Herreros, Clara - Technician
- Okeke Infante, Isabel Chinyere - PhD Student
- Pulido Navarro, Aurora - Technician
- Tello Rodríguez, Sandra - PhD Student
- Toribio López, Francisco René - Postdoctoral Fellow
- Vazquez, María Magdalena - Postdoctoral Fellow
Plants are sessile organisms that grow anchored through their root system to the soil. Since they lack the capacity to change their location, plants are forced to cope with the environmental conditions they are exposed to. To do it, plants have evolved highly sophisticated mechanisms to get adapted to the environmental challenges. These mechanisms operate at different molecular levels, assuring, among other things, the proper expression, accumulation and functionality of essential proteins involved in promoting plant adaptation to the ever-changing environmental conditions. For this, plants are able to finely regulate and coordinate two main processes under the conditions imposed by the environment: translation and protein folding.
Both processes, translation and protein folding, show a dual regulation in response to stress. On the one hand, general translation and protein folding are inhibited in response to adverse conditions. However, on the other hand, plants count with mechanisms that, under the conditions of general inhibition, allow the translation and preserve the folding of specific mRNAs and proteins that are crucial for promoting tolerance to stress. Despite this dual regulation being widely reported, the identity of the mRNAs/proteins and the mechanisms that allow their selective translation and folding under stress are mostly unknown. In this context, our lab aims at contributing to increase our knowledge of how plants modulate translation and protein folding in response to environmental cues in plants.
It is well stablished that environmental conditions affect multiple aspects of gene expression, including general and selective translation and protein folding, allowing plants to synthetize and maintain the functionality and activity of key proteins involved in the adaptation to stress. Although we already know that these two processes are pivotal for plant adaptation, we are still far for understanding the mechanisms and the identity of the mRNAs and proteins subjected to this selective regulation.
Selective translation in response to environmental cues
Our lab has implemented different techniques (such as in vivo labeling of de novo synthetized proteins, Ribo-seq analysis, polysomal profiling, etc.) to allow the identification of those mRNAs that are selectively regulated at the translational level (and so, highly susceptible to play an important function) during specific stages of development and in response to environmental cues. Regarding environmental stresses, our lab has focused on the analysis of how plants acclimate to heat and are able, through this acclimation, to cope with severe high temperature stresses. However, we are also currently analyzing the effects on translation of other abiotic stresses. In addition, we are studying the effect of the simultaneous incidence of biotic and abiotic stresses.
Identification of new translation regulators in plants
Translation is a highly conserved process. Nevertheless, our research and that of other laboratories have shown that plants possess unique mechanisms that allow them to modulate translation under specific environmental cues. One clear example of such specific mechanism, which has been recently uncovered in our lab, is CERES (Toribio et al., 2019). CERES is a non-canonical translational regulator, which enhances the general and selective translation of messenger RNAs at specific stages of the diel cycle, when the metabolic and energetic conditions of the plant (which are mainly determined by photosynthesis) are at their maximum level. Following this discovery, our lab is currently focused on the identification of new regulators of translation in response to light and multistresses.
Role of CERES in the coordination of translation with the energy status in plants and comparison of CERES with other mechanisms that regulate translation, such as the binding of the 4E-BPs to eIF4E, which in mammals inhibits translation under nutritional shortage. As shown, CERES, through its interaction with eIF4E, eIF4A and eIF3, promotes translation under favorable light conditions in plants (Toribio et al., 2019).
Deciphering how plants selectively preserve the folding of key proteins involved in plant development and response to stress. Analysis of the role of HOP co-chaperones in this process
Some proteins are assisted in their folding by chaperones and co-chaperones. Among them, HSP90 and its co-chaperones have been involved in the selective folding of important signaling proteins in mammals and yeast; however, the identity of the client proteins and processes affected by the HSP90 and its co-chaperones is extremely scarce in plants. In an attempt to analyze the relevance of selective protein folding in response to different environmental cues, we have analyzed the role of the co-chaperones HOP (HSP70-HSP90 organizing proteins) in different stress conditions. In such a way, we have demonstrated that HOP proteins play a main role in plant response to ER stress response (Fernández-Bautista et al 2017), in long-term acquired thermotolerance (LAT) (Fernández-Bautista et al 2018), plant defense (Muñoz et al, 2021) and in salt stress (Mangano et al., 2023).
HOP proteins play a major role in long term-acquired thermotolerance (LAT) in plants. Growth of the hop1 hop2 hop3 triple mutant, the hsfa2 mutant (a mutant with a well-known hypersensitivity to heat stress, included as a positive control) and Col-0 (the wild-type genotype) under control (A) and under LAT conditions (B) (Fernández-Bautista et al 2018).
Remarkably, recent results obtained in the lab have demonstrated that the function of HOP is not only circumscribed to the response to stress, but that, indeed, these proteins are also involved in different developmental and adaptative responses, acting as hubs in hormonal signaling in plants. In fact, we have recently reported that different members of the HOP family bind to the F-box proteins COI1, TIR1 and SLY2 and regulate COI1 activity and TIR1 and SLY2 stability. Moreover, we have reported that HOP proteins play important roles in jasmonic acid (JA), auxin and gibberellin (GA) signaling and in processes associated to these hormonal networks, such as plant defense against Tetranychus urticae infestation, lateral root formation, thermomorphogenesis or germination, among others (Muñoz et al., 2021, Muñoz et al., 2022; Mangano et al., 2023).
HOP proteins play a main role in the JA, auxin and GA hormonal pathways and associated processes by binding and regulating the activity and/or stability of the F-box proteins COI1, TIR1 and SLY2 (Muñoz et al., 2021, Muñoz et al., 2022; Mangano et al., 2023).
Despite the fact that we have made important progresses in understanding the relevance of selective folding regulation in plants in response to environmental cues, the identified client proteins of this regulation are probably only the tip of the iceberg. Based on this, our lab is developing new strategies to identify those proteins selectively folded by HOP and other co-chaperones under different single conditions and in response to multistresses in plants and to study the relevance of their selective folding in the response.
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2020-T1/BIO-19900. Unraveling the role of CERES and MRF1 interactors in translation regulation in response to light. 16/01/2022-31/12/2025 Atraction Call 2021, CAM, Spain. IP: Esther Novo Uzal.
RTI2018-095946-B-I00 Analysis of the role of HOP during thermomorphogenesis and its biotechnological application 01/01/2019 - 31/12/2021. AEI, Spain. IP: M. Mar Castellano.
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