Characterization of mRNA populations associatedwith the translational machinery (translatome)is shedding light on the molecular mechanisms ofplant environmental responses. The work presentedby Meteignier et  al. (2017) describes how selectivechanges in translation modulate the transitionfrom growth to defense responses in Arabidopsis,revealing new similarities between plant and animalimmunity.Fil: Zanetti, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Blanco, Flavio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentin

Blanco, Flavio Antonio

Zanetti, María Eugenia

Journal of Experimental Botany

LAReferencia - Red Federada de Repositorios Institucionales de Publicaciones Científicas Latinoamericanas

 | 2077Yamasaki T, Yamakawa T, Yamane Y, Koike H, Satoh K, Katoh S. 2002. Temperature acclimation of photosynthesis and related changes in photosystem II electron transport in winter wheat. Plant Physiology 128, 1087–1097.Yamori W, Hikosaka K, Way DA. 2014. Temperature response of photosynthesis in C3, C4, and CAM plants: temperature acclimation and temperature adaptation. Photosynthesis Research 119, 101–117.Yamori W, Suzuki K, Noguchi K, Nakai M, Terashima I. 2006. Effects of Rubisco kinetics and Rubisco activation state on the temperature dependence of the photosynthetic rate in spinach leaves from contrasting growth temperatures. Plant, Cell & Environment 29, 1659–1670.Zhang XW, Wang JR, Ji MF, Milne RI, Wang MH, Liu JQ, Shi S, Yang SL, Zhao CM. 2015. Higher thermal acclimation potential of respiration but not photosynthesis in two alpine Picea taxa in contrast to two lowland congeners. PLoS One 10, e0123248.Zhou X, Liu X, Wallace LL, Luo Y. 2007. Photosynthetic and respiratory acclimation to experimental warming for four species in a tallgrass prairie ecosystem. Journal of Integrative Plant Biology 49, 270–281.Ziska LH. 2001. Growth temperature can alter the temperature dependent stimulation of photosynthesis by elevated carbon dioxide in Albutilon theophrasti. Physiologia Plantarum 111, 322–328.InsightTranslational switching from growth to defense – a common role for TOR in plant and mammalian immunity?María Eugenia Zanetti1,* and Flavio A. Blanco11 Instituto de Biotecnología y Biología Molecular, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-La Plata, CONICET, La Plata, Argentina* Correspondence: ezanetti@biol.unlp.edu.arCharacterization of mRNA populations associ-ated with the translational machinery (translatome) is shedding light on the molecular mechanisms of plant environmental responses. The work presented by Meteignier et  al. (2017) describes how selec-tive changes in translation modulate the transition from growth to defense responses in Arabidopsis, revealing new similarities between plant and animal immunity.Plants have developed sophisticated mechanisms to adjust their developmental programs in response to changes in their environment. This adaptation largely depends on selec-tive changes in gene expression, which include transcrip-tional and post-transcriptional control. Transcriptional changes provide a long-term response and, usually, are triggered by a signaling pathway initiated by signal percep-tion that culminates in the activation of  transcription fac-tors in the nucleus. Transcriptome (the population of  total cellular mRNAs) studies have enabled the identification of genes that are crucial for adaptation in numerous plant spe-cies. However, mRNA abundance and protein levels do not always correlate due to co- and post-transcriptional mecha-nisms controlling gene expression. Among such post-tran-scriptional mechanisms, mRNA translation plays a crucial role in controlling the amount of  protein present in a cell or tissue. Translational control has been observed in a number of  developmental processes in plants, as well as in response to environmental cues.During the past decade, an increasing number of studies have focused on changes in the translatome (the population of actively translating mRNAs) during phase-transitions or perturbation caused by endogenous or exogenous signals. From these studies we know that translational control can be global, affecting most cellular mRNAs, or selective, affect-ing just a subset. Global translational repression has been observed during stresses that produce a cellular ‘energy cri-sis’, such as hypoxia (Branco-Price et al., 2005; Branco-Price et al., 2008; Mustroph et al., 2009), heat (Yanguez et al., 2013), and drought (Kawaguchi and Bailey-Serres, 2002; Kawaguchi et  al., 2004; Lei et  al., 2015). On the other hand, selective translational regulation has been associated with dark/light transitions (Juntawong and Bailey-Serres, 2012), photomor-phogenesis (Liu et al., 2013), daily clock cycles (Missra et al., 2015), and symbiosis with nitrogen-fixing bacteria (Reynoso et al., 2013).Meteignier et  al. (2017) show that selective translational control also occurs during plant immunity. A  remarkable characteristic of translational regulation is that it enables rapid adjustment of the proteome using the existing tran-scriptome, thus providing cells or tissues with a fast and flex-ible response for adapting to changes in their environment, as in the case of the hypersensitive response triggered by some plant pathogens. This rapid response is frequently achieved by controlling the initiation step of translation, i.e. by increasing or decreasing the number of molecules of individual tran-scripts that are recruited to the translational machinery with-out a change in transcript abundance or even, in some cases, with an opposite change in transcript abundance.© The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.  This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.2078 |Translational control of immunity in plants and animalsPlant immunity against pathogens relies on mechanisms that allow host cells to perceive pathogens and mount a rapid and effective response that limits their spread. The work of Meteignier et al. (2017) used TRAP-seq technology (Box 1) to characterize the rapid and selective translational response of Arabidopsis plants upon activation of the effector-trig-gered immunity (ETI) response. The authors found that, dur-ing short intervals following ETI activation, the translational and transcriptional responses were uncoupled, especially for many of the genes that are negatively regulated. Accordingly, those genes with uncoupled transcription/translation showed the larger changes in translational efficiency upon activation of ETI. Genes involved in photosynthesis, gravi- and photo-tropism, auxin metabolism and carbohydrate biosynthesis were down-regulated at the translational level, whereas genes that participate in cell wall thickness, secondary metabolism and cell death were translationally up-regulated, revealing a reprogramming of the host cells, which appear to undergo a switch from growth and development to defense (Box 2).Box 1. TRAP-seq methodologyPioneer translatome studies used ultracentrifugation through sucrose-density gradients to fractionate 40S and 60S ribosomal subunits, 80S monosomes and polyribosomes (polysomes) of different size (mRNAs with ≥2 ribosomes). Later on, a method based on affinity purification known as TRAP (Translating Ribosome Affinity Purification) was developed for plants (Zanetti et al., 2005), mammals (Heiman et al., 2008) and yeast (Halbeisen and Gerber, 2009). In plants, TRAP-seq is based on the expression of FLAG-tagged Ribosomal Protein Large subunit 18 (RPL18), which is incorporated into translating ribosomes, providing a means of affinity-puri-fying ribosomes, polysomes and associated mRNAs. The population of mRNAs present in TRAP samples is then analyzed by direct RNA sequencing. In parallel, total cellular mRNAs from the same tissue and conditions are analyzed by RNA-seq, thus allowing a comparison of transcriptional and translational changes in gene expression, as well as an estimation of the translational efficiency (the Log2 ratio of the amount of polysome-associated RNA to the total cellular amount of RNA for a given mRNA). More recently, a technique that precisely maps the ribosome-protected regions in an individual mRNA, known as ribosome footprinting or ribo-some profiling (Ingolia et al., 2009), has been combined with TRAP and applied to gain insights into mechanistic aspects of translational control in plants (Juntawong et al., 2014). | 2079A number of novel genes involved in plant immunity were identified through this translatomic analysis, including Phosphorylcholine cytidylyltransferase 2 (CCT2), the calos-sin-like protein BIG, and CBL-Interacting protein kinase 5 (CIPK5), and these were functionally validated by reverse genetics. Interestingly, Target of Rapamycin (TOR), which regulates plant development by restructuring cell growth and carbon/nitrogen metabolism (Ren et  al., 2012), dramatically decreased its translational efficiency upon activation of ETI. Moreover, Meteignier and co-workers showed that silencing TOR decreased plant susceptibility to the pathogenic bacterium Pseudomonas syringae and the oomycete Hyaloperonospora arabidopsidis, suggesting that TOR acts as a negative regula-tor of disease resistance. Previous studies have shown that the transcriptome of plants with reduced TOR activity is enriched in transcripts involved in defense responses and innate immu-nity, supporting the notion that TOR negatively regulates defense responses. This suggest that low levels of TOR are associated with reprogramming the growth-to-defense transi-tion. In addition, reduction of TOR activity decreased anab-olism and increased catabolism (Caldana et al., 2013), which might be linked to the reorientation of cellular activities to gen-erate the energy required to mount a defense response.The identification of  TOR as a negative regulator of plant immunity has novel implications concerning the similarities between plant and animal immune systems. In mammals, the TOR pathway integrates exogenous sig-nals with endogenous cues such as cellular energy status, Box  2. Transcriptional and translational changes mediated by activation of NB-LRR receptors during the ETI responsePlant defense is based on two recognition systems. Pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs, such as the flagellin protein) to induce PAMP-triggered immunity (PTI), a level of defense that can be overcome by the pro-duction of pathogen effectors, such as avrRpm1, which is produced by Pseudomonas syrin-gae and introduced into the plant cell by the type III secretion system. The second layer of defense relies on the recognition of these effectors by receptors, such as the NB-LRR RPM1 of Arabidopsis, triggering effector-triggered immunity (ETI), which induces a similar response to PTI, but more quickly and robustly. ETI can lead to the hypersensitive response (HR), a form of cell death limiting the spread of bio- and hemibio-trophic pathogens. Signaling events down-stream of receptor activation are poorly understood, but they include modulation of transcriptional responses in the nucleus. Meteignier et al. (2017) reveal that ETI also leads to changes in the translational status of pre-existing mRNAs in the cytoplasm. Translationally regulated mRNAs include those encoding HR-associated proteins, Target of Rapamycin (TOR) and other proteins such as Phosphorylcholine cytidylyltransferase 2 (CCT2), the calossin-like protein BIG and CBL-Interacting protein kinase 5 (CIPK5). TOR seems to affect the transition from growth to defense, whereas the other genes might act as positive or negative regulators of defense responses.2080 |hormones and growth factors to stimulate cell growth, pro-liferation and differentiation. This pathway also plays a cen-tral role in the translational control of  innate or adaptive immunity (Piccirillo et  al., 2014). The best-characterized translational targets of  TOR in mammals are 4E-binding proteins (4E-BPs), which act as translational suppressors by binding the eukaryotic initiation factor 4E (eIF4E, the cap-binding subunit of  the eIF4F complex), preventing the formation of  the eIF4F complex. The TOR–4EBPeIF4E module influences the translation of  a subset of  mRNAs referred to as ‘eIF4E sensitive’, including those encoding proteins involved in immunity, such as the transcription factor interferon regulatory factor 7 (IRF7). Mice defi-cient in 4EBPs are less susceptible than the wild type to viral infection and unable to suppress the translation of the IRF7 transcript upon virus-induced inhibition of  TOR signaling (Colina et al., 2008). Although the translational targets of  TOR signaling in plants are not known yet, this pathway seems to play an active role in the switch from growth to immunity in both plants and mammals. Further studies are required to elucidate whether TOR influences the selective translation of  mRNAs during plant immunity and the potential targets of  translational control of  this pathway in plants.Looking forward: mechanistic insights into translational control in plantsMost of  the high-throughput analyses have centered on the characterization of  transcriptomes, but application of  new techniques, such as TRAP-seq and Ribo-seq, have started to reveal the importance of  translation in the regulation of gene expression. The study of  Meteignier et al. nicely illus-trates how the analysis of  translatomes might contribute to the identification of  new players with important functions in the adaptation and response of  plants to environmental challenges. Many biological processes could be fully under-stood only through the characterization of  gene expression changes at different levels, complementing transcriptome studies with the analysis of  translatomes, ribosome foot-prints, degradomes and proteomes. It is expected that the partial contribution of  each regulatory level will be differ-ent for each process depending on the complexity and the time of  the response. Rapid responses, such as the hyper-sensitive response, seem to rely on changes at the post-tran-scriptional level, activating the translation of  pre-existing mRNAs that are stored inside the cell such that they are ready at the moment of  challenge, generating a functional protein in a short time-frame. In addition, it is necessary to study these processes in the individual cell types involved in the response, which can be achieved by combining TRAP with the use of  cell-specific promoters (Mustroph et  al., 2009). Also, to understand better how genes are regulated at the translational level it will be crucial to identify the cis-regulatory elements present in each transcript, as well as the trans-acting RNA-binding protein, which influence its selective association with the translational machinery and, more importantly, how its translational status can be mod-ulated to generate the dynamic response required to adapt rapidly to changes in the environment. A preliminary study by Meteignier, Moffett and colleagues analyzing their candi-dates for the presence of  shared elements in the untranslated regions is now available (Munusamy et al., 2017).Key words: Effector-triggered immunity (ETI), NB-LRR proteins, plant defense, target of rapamycin (TOR), translation.Journal of Experimental Botany, Vol. 68 No. 9 pp. 2077-2081, 2017  doi: 10.1093/jxb/erx120ReferencesBranco-Price C, Kaiser KA, Jang CJ, Larive CK, Bailey-Serres J. 2008. Selective mRNA translation coordinates energetic and metabolic adjustments to cellular oxygen deprivation and reoxygenation in Arabidopsis thaliana. The Plant Journal 56, 743–755.Branco-Price C, Kawaguchi R, Ferreira RB, Bailey-Serres J. 2005. Genome-wide analysis of transcript abundance and translation in Arabidopsis seedlings subjected to oxygen deprivation. Annals of Botany 96, 647–660.Caldana C, Li Y, Leisse A, Zhang Y, Bartholomaeus L, Fernie AR, Willmitzer L, Giavalisco P. 2013. Systemic analysis of inducible target of rapamycin mutants reveal a general metabolic switch controlling growth in Arabidopsis thaliana. The Plant Journal 73, 897–909.Colina R, Costa-Mattioli M, Dowling RJ, et al. 2008. Translational control of the innate immune response through IRF-7. Nature 452, 323–328.Halbeisen RE, Gerber AP. 2009. Stress-dependent coordination of transcriptome and translatome in yeast. PLoS Biology 7, e1000105.Heiman M, Schaefer A, Gong S, et al. 2008. A translational profiling approach for the molecular characterization of CNS cell types. Cell 135, 738–748.Ingolia NT, Ghaemmaghami S, Newman JR, Weissman JS. 2009. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324, 218–223.Juntawong P, Bailey-Serres J. 2012. Dynamic light regulation of translation status in Arabidopsis thaliana. Frontiers in Plant Science 3, 66.Juntawong P, Girke T, Bazin J, Bailey-Serres J. 2014. Translational dynamics revealed by genome-wide profiling of ribosome footprints in Arabidopsis. Proceedings of the National Academy of Sciences, USA 111, E203–212.Kawaguchi R, Bailey-Serres J. 2002. Regulation of translational initiation in plants. Current Opinion in Plant Biology 5, 460–465.Kawaguchi R, Girke T, Bray EA, Bailey-Serres J. 2004. Differential mRNA translation contributes to gene regulation under non-stress and dehydration stress conditions in Arabidopsis thaliana. The Plant Journal 38, 823–839.Lei L, Shi J, Chen J, et al. 2015. Ribosome profiling reveals dynamic translational landscape in maize seedlings under drought stress. The Plant Journal 84, 1206–1218.Liu MJ, Wu SH, Wu JF, Lin WD, Wu YC, Tsai TY, Tsai HL, Wu SH. 2013. Translational landscape of photomorphogenic Arabidopsis. The Plant Cell 25, 3699–3710.Meteignier LV, El Oirdi M, Cohen M, et al. 2017. Translatome analysis of an NB-LRR immune response identifies important contributors to plant immunity in Arabidopsis. Journal of Experimental Botany 68, 2333–2344.Missra A, Ernest B, Lohoff T, Jia Q, Satterlee J, Ke K, von Arnim AG. 2015. The circadian clock modulates global daily cycles of mRNA ribosome loading. The Plant Cell 27, 2582–2599.Munusamy P, Zolotarov Y, Meteignier LV, Moffett P, Strömvik MV. 2017. De novo computational identification of stress-related sequence motifs and microRNA target sites in untranslated regions of a plant translatome. Scientific Reports 7, 43861.Mustroph A, Zanetti ME, Jang CJ, Holtan HE, Repetti PP, Galbraith DW, Girke T, Bailey-Serres J. 2009. Profiling translatomes of discrete  | 2081cell populations resolves altered cellular priorities during hypoxia in Arabidopsis. Proceedings of the National Academy of Sciences, USA 106, 18843–18848.Piccirillo CA, Bjur E, Topisirovic I, Sonenberg N, Larsson O. 2014. Translational control of immune responses: from transcripts to translatomes. Nature Immunology 15, 503–511.Ren M, Venglat P, Qiu S, et al. 2012. Target of rapamycin signaling regulates metabolism, growth, and life span in Arabidopsis. The Plant Cell 24, 4850–4874.Reynoso MA, Blanco FA, Bailey-Serres J, Crespi M, Zanetti ME. 2013. Selective recruitment of mRNAs and miRNAs to polyribosomes in response to rhizobia infection in Medicago truncatula. The Plant Journal 73, 289–301.Yángüez E, Castro-Sanz AB, Fernández-Bautista N, Oliveros JC, Castellano MM. 2013. Analysis of genome-wide changes in the translatome of Arabidopsis seedlings subjected to heat stress. PLoS One 8, e71425.Zanetti ME, Chang IF, Gong F, Galbraith DW, Bailey-Serres J. 2005. Immunopurification of polyribosomal complexes of Arabidopsis for global analysis of gene expression. Plant Physiology 138, 624–635.

English

Translational switching from growth to defense – a common role for TOR in plant and mammalian immunity?

María Eugenia Zanetti

Flavio A. Blanco

Crossref

Characterization of mRNA populations associated with the translational machinery (translatome) is shedding light on the molecular mechanisms of plant environmental responses. The work presented by Meteignier et al. (2017) describes how selective changes in translation modulate the transition from growth to defense responses in Arabidopsis, revealing new similarities between plant and animal immunity.Facultad de Ciencias Exacta

El Servicio de Difusión de la Creación Intelectual

 | 2077
Yamasaki T, Yamakawa T, Yamane Y, Koike H, Satoh K, Katoh S. 2002. 
Temperature acclimation of photosynthesis and related changes in photosystem 
II electron transport in winter wheat. Plant Physiology 128, 1087–1097.
Yamori W, Hikosaka K, Way DA. 2014. Temperature response of 
photosynthesis in C3, C4, and CAM plants: temperature acclimation and 
temperature adaptation. Photosynthesis Research 119, 101–117.
Yamori W, Suzuki K, Noguchi K, Nakai M, Terashima I. 2006. Effects 
of Rubisco kinetics and Rubisco activation state on the temperature 
dependence of the photosynthetic rate in spinach leaves from contrasting 
growth temperatures. Plant, Cell & Environment 29, 1659–1670.
Zhang XW, Wang JR, Ji MF, Milne RI, Wang MH, Liu JQ, Shi S, Yang 
SL, Zhao CM. 2015. Higher thermal acclimation potential of respiration 
but not photosynthesis in two alpine Picea taxa in contrast to two lowland 
congeners. PLoS One 10, e0123248.
Zhou X, Liu X, Wallace LL, Luo Y. 2007. Photosynthetic and respiratory 
acclimation to experimental warming for four species in a tallgrass prairie 
ecosystem. Journal of Integrative Plant Biology 49, 270–281.
Ziska LH. 2001. Growth temperature can alter the temperature 
dependent stimulation of photosynthesis by elevated carbon dioxide in 
Albutilon theophrasti. Physiologia Plantarum 111, 322–328.
Insight
Translational switching from growth to defense – a common 
role for TOR in plant and mammalian immunity?
María Eugenia Zanetti1,* and Flavio A. Blanco1
1 Instituto de Biotecnología y Biología Molecular, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-La Plata, 
CONICET, La Plata, Argentina
* Correspondence: ezanetti@biol.unlp.edu.ar
Characterization of mRNA populations associ-
ated with the translational machinery (translatome) 
is shedding light on the molecular mechanisms of 
plant environmental responses. The work presented 
by Meteignier et  al. (2017) describes how selec-
tive changes in translation modulate the transition 
from growth to defense responses in Arabidopsis, 
revealing new similarities between plant and animal 
immunity.
Plants have developed sophisticated mechanisms to adjust 
their developmental programs in response to changes in 
their environment. This adaptation largely depends on selec-
tive changes in gene expression, which include transcrip-
tional and post-transcriptional control. Transcriptional 
changes provide a long-term response and, usually, are 
triggered by a signaling pathway initiated by signal percep-
tion that culminates in the activation of  transcription fac-
tors in the nucleus. Transcriptome (the population of  total 
cellular mRNAs) studies have enabled the identification of 
genes that are crucial for adaptation in numerous plant spe-
cies. However, mRNA abundance and protein levels do not 
always correlate due to co- and post-transcriptional mecha-
nisms controlling gene expression. Among such post-tran-
scriptional mechanisms, mRNA translation plays a crucial 
role in controlling the amount of  protein present in a cell or 
tissue. Translational control has been observed in a number 
of  developmental processes in plants, as well as in response 
to environmental cues.
During the past decade, an increasing number of studies 
have focused on changes in the translatome (the population 
of actively translating mRNAs) during phase-transitions or 
perturbation caused by endogenous or exogenous signals. 
From these studies we know that translational control can 
be global, affecting most cellular mRNAs, or selective, affect-
ing just a subset. Global translational repression has been 
observed during stresses that produce a cellular ‘energy cri-
sis’, such as hypoxia (Branco-Price et al., 2005; Branco-Price 
et al., 2008; Mustroph et al., 2009), heat (Yanguez et al., 2013), 
and drought (Kawaguchi and Bailey-Serres, 2002; Kawaguchi 
et  al., 2004; Lei et  al., 2015). On the other hand, selective 
translational regulation has been associated with dark/light 
transitions (Juntawong and Bailey-Serres, 2012), photomor-
phogenesis (Liu et al., 2013), daily clock cycles (Missra et al., 
2015), and symbiosis with nitrogen-fixing bacteria (Reynoso 
et al., 2013).
Meteignier et  al. (2017) show that selective translational 
control also occurs during plant immunity. A  remarkable 
characteristic of translational regulation is that it enables 
rapid adjustment of the proteome using the existing tran-
scriptome, thus providing cells or tissues with a fast and flex-
ible response for adapting to changes in their environment, as 
in the case of the hypersensitive response triggered by some 
plant pathogens. This rapid response is frequently achieved by 
controlling the initiation step of translation, i.e. by increasing 
or decreasing the number of molecules of individual tran-
scripts that are recruited to the translational machinery with-
out a change in transcript abundance or even, in some cases, 
with an opposite change in transcript abundance.
© The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.  
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), 
which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
2078 |
Translational control of immunity in plants 
and animals
Plant immunity against pathogens relies on mechanisms that 
allow host cells to perceive pathogens and mount a rapid 
and effective response that limits their spread. The work of 
Meteignier et al. (2017) used TRAP-seq technology (Box 1) 
to characterize the rapid and selective translational response 
of Arabidopsis plants upon activation of the effector-trig-
gered immunity (ETI) response. The authors found that, dur-
ing short intervals following ETI activation, the translational 
and transcriptional responses were uncoupled, especially for 
many of the genes that are negatively regulated. Accordingly, 
those genes with uncoupled transcription/translation showed 
the larger changes in translational efficiency upon activation 
of ETI. Genes involved in photosynthesis, gravi- and photo-
tropism, auxin metabolism and carbohydrate biosynthesis 
were down-regulated at the translational level, whereas genes 
that participate in cell wall thickness, secondary metabolism 
and cell death were translationally up-regulated, revealing a 
reprogramming of the host cells, which appear to undergo a 
switch from growth and development to defense (Box 2).
Box 1. TRAP-seq methodology
Pioneer translatome studies used ultracentrifugation through sucrose-density gradients to 
fractionate 40S and 60S ribosomal subunits, 80S monosomes and polyribosomes (polysomes) 
of different size (mRNAs with ≥2 ribosomes). Later on, a method based on affinity purification 
known as TRAP (Translating Ribosome Affinity Purification) was developed for plants (Zanetti 
et al., 2005), mammals (Heiman et al., 2008) and yeast (Halbeisen and Gerber, 2009). In plants, 
TRAP-seq is based on the expression of FLAG-tagged Ribosomal Protein Large subunit 18 
(RPL18), which is incorporated into translating ribosomes, providing a means of affinity-puri-
fying ribosomes, polysomes and associated mRNAs. The population of mRNAs present in 
TRAP samples is then analyzed by direct RNA sequencing. In parallel, total cellular mRNAs 
from the same tissue and conditions are analyzed by RNA-seq, thus allowing a comparison of 
transcriptional and translational changes in gene expression, as well as an estimation of the 
translational efficiency (the Log2 ratio of the amount of polysome-associated RNA to the total 
cellular amount of RNA for a given mRNA). More recently, a technique that precisely maps the 
ribosome-protected regions in an individual mRNA, known as ribosome footprinting or ribo-
some profiling (Ingolia et al., 2009), has been combined with TRAP and applied to gain insights 
into mechanistic aspects of translational control in plants (Juntawong et al., 2014).
 | 2079
A number of novel genes involved in plant immunity 
were identified through this translatomic analysis, including 
Phosphorylcholine cytidylyltransferase 2 (CCT2), the calos-
sin-like protein BIG, and CBL-Interacting protein kinase 5 
(CIPK5), and these were functionally validated by reverse 
genetics. Interestingly, Target of Rapamycin (TOR), which 
regulates plant development by restructuring cell growth and 
carbon/nitrogen metabolism (Ren et  al., 2012), dramatically 
decreased its translational efficiency upon activation of ETI. 
Moreover, Meteignier and co-workers showed that silencing 
TOR decreased plant susceptibility to the pathogenic bacterium 
Pseudomonas syringae and the oomycete Hyaloperonospora 
arabidopsidis, suggesting that TOR acts as a negative regula-
tor of disease resistance. Previous studies have shown that the 
transcriptome of plants with reduced TOR activity is enriched 
in transcripts involved in defense responses and innate immu-
nity, supporting the notion that TOR negatively regulates 
defense responses. This suggest that low levels of TOR are 
associated with reprogramming the growth-to-defense transi-
tion. In addition, reduction of TOR activity decreased anab-
olism and increased catabolism (Caldana et al., 2013), which 
might be linked to the reorientation of cellular activities to gen-
erate the energy required to mount a defense response.
The identification of  TOR as a negative regulator of 
plant immunity has novel implications concerning the 
similarities between plant and animal immune systems. 
In mammals, the TOR pathway integrates exogenous sig-
nals with endogenous cues such as cellular energy status, 
Box  2. Transcriptional and translational changes mediated by activation of NB-LRR 
receptors during the ETI response
Plant defense is based on two recognition systems. Pattern recognition receptors (PRRs) 
recognize pathogen-associated molecular patterns (PAMPs, such as the flagellin protein) to 
induce PAMP-triggered immunity (PTI), a level of defense that can be overcome by the pro-
duction of pathogen effectors, such as avrRpm1, which is produced by Pseudomonas syrin-
gae and introduced into the plant cell by the type III secretion system. The second layer of 
defense relies on the recognition of these effectors by receptors, such as the NB-LRR RPM1 
of Arabidopsis, triggering effector-triggered immunity (ETI), which induces a similar response 
to PTI, but more quickly and robustly. ETI can lead to the hypersensitive response (HR), a 
form of cell death limiting the spread of bio- and hemibio-trophic pathogens. Signaling events 
down-stream of receptor activation are poorly understood, but they include modulation of 
transcriptional responses in the nucleus. Meteignier et al. (2017) reveal that ETI also leads to 
changes in the translational status of pre-existing mRNAs in the cytoplasm. Translationally 
regulated mRNAs include those encoding HR-associated proteins, Target of Rapamycin (TOR) 
and other proteins such as Phosphorylcholine cytidylyltransferase 2 (CCT2), the calossin-like 
protein BIG and CBL-Interacting protein kinase 5 (CIPK5). TOR seems to affect the transition 
from growth to defense, whereas the other genes might act as positive or negative regulators 
of defense responses.
2080 |
hormones and growth factors to stimulate cell growth, pro-
liferation and differentiation. This pathway also plays a cen-
tral role in the translational control of  innate or adaptive 
immunity (Piccirillo et  al., 2014). The best-characterized 
translational targets of  TOR in mammals are 4E-binding 
proteins (4E-BPs), which act as translational suppressors 
by binding the eukaryotic initiation factor 4E (eIF4E, the 
cap-binding subunit of  the eIF4F complex), preventing the 
formation of  the eIF4F complex. The TOR–4EBPeIF4E 
module influences the translation of  a subset of  mRNAs 
referred to as ‘eIF4E sensitive’, including those encoding 
proteins involved in immunity, such as the transcription 
factor interferon regulatory factor 7 (IRF7). Mice defi-
cient in 4EBPs are less susceptible than the wild type to 
viral infection and unable to suppress the translation of 
the IRF7 transcript upon virus-induced inhibition of  TOR 
signaling (Colina et al., 2008). Although the translational 
targets of  TOR signaling in plants are not known yet, this 
pathway seems to play an active role in the switch from 
growth to immunity in both plants and mammals. Further 
studies are required to elucidate whether TOR influences 
the selective translation of  mRNAs during plant immunity 
and the potential targets of  translational control of  this 
pathway in plants.
Looking forward: mechanistic insights into 
translational control in plants
Most of  the high-throughput analyses have centered on the 
characterization of  transcriptomes, but application of  new 
techniques, such as TRAP-seq and Ribo-seq, have started 
to reveal the importance of  translation in the regulation of 
gene expression. The study of  Meteignier et al. nicely illus-
trates how the analysis of  translatomes might contribute to 
the identification of  new players with important functions 
in the adaptation and response of  plants to environmental 
challenges. Many biological processes could be fully under-
stood only through the characterization of  gene expression 
changes at different levels, complementing transcriptome 
studies with the analysis of  translatomes, ribosome foot-
prints, degradomes and proteomes. It is expected that the 
partial contribution of  each regulatory level will be differ-
ent for each process depending on the complexity and the 
time of  the response. Rapid responses, such as the hyper-
sensitive response, seem to rely on changes at the post-tran-
scriptional level, activating the translation of  pre-existing 
mRNAs that are stored inside the cell such that they are 
ready at the moment of  challenge, generating a functional 
protein in a short time-frame. In addition, it is necessary to 
study these processes in the individual cell types involved in 
the response, which can be achieved by combining TRAP 
with the use of  cell-specific promoters (Mustroph et  al., 
2009). Also, to understand better how genes are regulated 
at the translational level it will be crucial to identify the cis-
regulatory elements present in each transcript, as well as 
the trans-acting RNA-binding protein, which influence its 
selective association with the translational machinery and, 
more importantly, how its translational status can be mod-
ulated to generate the dynamic response required to adapt 
rapidly to changes in the environment. A preliminary study 
by Meteignier, Moffett and colleagues analyzing their candi-
dates for the presence of  shared elements in the untranslated 
regions is now available (Munusamy et al., 2017).
Key words: Effector-triggered immunity (ETI), NB-LRR proteins, plant 
defense, target of rapamycin (TOR), translation.
Journal of Experimental Botany, Vol. 68 No. 9 pp. 2077-2081, 2017  
doi: 10.1093/jxb/erx120
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Translational switching from growth to defense - a common role for TOR in plant and mammalian immunity?

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Translational switching from growth to defense – a common role for TOR in plant and mammalian immunity?

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