TOR in acTIon · TRANSLATION INITIATION CONTROL IN PLANTS: THE ROLE OF TOR (TARGET OF RAPAMYCIN)

TRANSLATION INITIATION CONTROL IN PLANTS: THE ROLE OF TOR (TARGET OF RAPAMYCIN)

Protein synthesis-Translation is the most energy-consuming cellular process. The kinase Target of Rapamycin (TOR) is a master-regulator of translation in all eukaryotes. The mechanism is well-studied how TOR regulates translation in animals, which is largely unknown in plants. In this project, we identified two repressor proteins At4EBP1/2 in plants under the control of TOR. We characterized how TOR controls At4EBP1/2 and client mRNAs of At4EBP1/2. Especially At4EBP2 plays an important role in plant meristem activity. This predominantly post-embryonic process relies on the continuous activity of pluripotent stem cells at the meristem, where TOR is exclusively expressed. Engineering At4EBP2 will lead to precise control of meristem activity and further plant growth and development tackling the changing environment. More interestingly, the primary structure of plant 4EBPs is different from mammalian 4EBPs. Our research provides new insight of impinging 4EBPs in many different types of human diseases, e.g. cancer. In this project, our result filled the knowledge gap between TOR and cap-dependent translation initiation control in planta. Mammalian 4EBPs have been studied extensively and alterations in their proper functioning have been described in fatal diseases, including cancer. Yet, while comparing our newly discovered Arabidopsis 4EBPs and human 4EBPs, we realized that some mechanisms existing in plants are not described in humans and vice versa, suggesting that each system could benefit from the other to identify and characterize novel regulatory mechanisms. In addition, the client mRNAs identified in this project as 4EBP targets will be an important plant engineering strategy to increase protein production and thus improve crop productivity and stress tolerance. In summary, we discovered and characterized Arabidopsis 4EBPs whose primary structure differs from mammalian 4EBPs. We studied 4EBP interaction with the cap-binding complex, phosphorylation by TOR and biological significance for plant development. Client mRNAs regulated by the TOR-4EBP pathway have been identified. Several over-expression and knock-out/down lines of 4EBPs have been generated, which will be further used for polysomal RNA-seq and ribosome profiling (ribo-seq). Dr. Dong has finished most of the proposed work on the project and the main results are in preparation for publication.

Data: CORDIS, © European Union