Control of translation during the unfolded protein response in maize seedlings: Life without PERKs

Abstract

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) defines a condition called ER stress that induces the unfolded protein response (UPR). The UPR in mammalian cells attenuates protein synthesis initiation, which prevents the piling up of misfolded proteins in the ER. Mammalian cells rely on Protein Kinase RNA‐Like Endoplasmic Reticulum Kinase (PERK) phosphorylation of eIF2α to arrest protein synthesis, however, plants do not have a PERK homolog, so the question is whether plants control translation in response to ER stress. We compared changes in RNA levels in the transcriptome to the RNA levels protected by ribosomes and found a decline in translation efficiency, including many UPR genes, in response to ER stress. The decline in translation efficiency is due to the fact that many mRNAs are not loaded onto polyribosomes (polysomes) in proportion to their increase in total RNA, instead some of the transcripts accumulate in stress granules (SGs). The RNAs that populate SGs are not derived from the disassembly of polysomes because protein synthesis remains steady during stress. Thus, the surge in transcription of UPR genes in response to ER stress is accompanied by the formation of SGs, and the sequestration of mRNAs in SGs may serve to temporarily relieve the translation load during ER stress.

Evolution of the unfolded protein response in plants

“…Mammals have protein kinase R (PKR)‐like endoplasmic reticulum kinase (PERK), which is missing in plants (Kanodia et al, 2020). Although PERK is a protein kinase, it is involved in metazoans in activating a transcriptional response by phosphorylating factors that ultimately activate the transcription of stress response genes (Harding, Zhang, Bertolotti, Zeng, & Ron, 2000).…”

“…Furthermore, there is evidence that eIF2α phosphorylation does not block translation initiation in plants (Browning & Bailey‐Serres, 2015; Zhigailov et al, 2020). So, although translation attenuation is a signature event in response to endoplasmic reticulum stress in metazoans, translation initiation is not attenuated in response to endoplasmic reticulum stress in plants (Izquierdo et al, 2018; Kamauchi, Nakatani, Nakano, & Urade, 2005; Kanodia et al, 2020).…”

“…* Cannot determine in maize whether the two IRE1 forms are more IRE1a-like or IRE1b-like. † Does not have consensus S1P cleavage sites required for mobilization via Regulated Intradomain Proteolysis [Colour figure can be viewed at wileyonlinelibrary.com] Mammals have protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), which is missing in plants (Kanodia et al, 2020).…”

A temporal hierarchy underpins the transcription factor–DNA interactome of the maize UPR

“…The bulk transcriptional changes in the UPR have been established in Arabidopsis (Martínez and Chrispeels, 2003), maize (Srivastava et al ., 2018; Kanodia et al ., 2020), and metazoan species (Travers et al ., 2000; Han et al ., 2013), but the identity and dynamics of the gene‐regulatory hubs underlying the progression of the ER stress responses are yet unmapped in any of these species. To fill this gap and identify the transcriptional regulators upstream of the UPR in maize, we sought to identify the TFs binding to the promoters of genes representing distinct phases of ER stress responses.…”

“…Upon ER stress, bZIP28 (after proteolysis in the Golgi apparatus) and bZIP60 (after IRE1‐mediated unconventional splicing) are translocated into the nucleus, where they control the expression of target genes, acting as master regulators. Orthologous genes encoding these core components have been identified or characterized in crops such as maize ( Zea mays ) (Li et al ., 2012; Srivastava et al ., 2018; Kanodia et al ., 2020) and rice ( Oryza sativa ) (Oono et al ., 2010; Hayashi et al ., 2012; Lu et al ., 2012; Qian et al ., 2018; Wang et al ., 2018b). Growing evidence, however, suggests that gene regulation of the UPR is more complex than previously thought.…”