Mammalian/mechanistic target of rapamycin (mTOR) regulates global protein synthesis through inactivation of eIF4E-binding proteins (m4E-BPs) in response to nutrient and energy availability. Until now, 4E-BPs have been considered as metazoan inventions, and how target of rapamycin (TOR) controls cap-dependent translation initiation in plants remains obscure. Here, we present short unstructured 4E-BP-like Arabidopsis proteins (4EBP1/4EBP2) that are non-homologous to m4E-BPs except for the eIF4E-binding motif and TOR phosphorylation sites. Unphosphorylated 4EBPs exhibit strong affinity toward eIF4Es and can inhibit formation of the cap-binding complex. Upon TOR activation, 4EBPs are phosphorylated, probably when bound directly to TOR, and likely relocated to ribosomes. 4EBPs can suppress a distinct set of mRNAs; 4EBP2 predominantly inhibits translation of core cell-cycle regulators CycB1;1 and CycD1;1, whereas 4EBP1 interferes with chlorophyll biosynthesis. Accordingly, 4EBP2 overexpression halts early seedling development, which is overcome by induction of Glc/Suc-TOR signaling. Thus, TOR regulates cap-dependent translation initiation by inactivating atypical 4EBPs in plants.
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