Export and translation of RNA under TOR signalling control

Group leader : Lyubov RYABOVA

Research area

Our laboratory is interested in uncovering the link between environmental signals (e.g., viruses and phytohormones), fundamental cellular processes (e.g., mRNA export, translation, a target of rapamycin (TOR) protein kinase signaling pathway), and plant growth and organogenesis.
A major topic in our group concerns the non-canonical mechanisms used to reinitiate translation on mRNAs that harbour upstream open reading frames (uORFs) within their leader regions. uORFs regulate expression of genes coding for potent proteins such as cytokines, protein kinases and transcription factors. The TOR signaling pathway connecting environmental perception to growth decisions positively regulates translation initiation in mammals. We found other routes of TOR function in planta when using the TOR upstream effector, the phytohormone auxin, that by triggering TOR activation up-regulates translation of uORF-containing mRNAs. However, the pathway is far from being elucidated. We shall address questions about novel TOR upstream effectors and downstream targets, and show their role in translation control in plants.
Toward this goal we study how these cellular translation pathways are hijacked by the Cauliflower mosaic virus (CaMV) to achieve translation of its 35S polycistronic mRNA via reinitiation. CaMV protein TAV that activates viral translation via activation of TOR serves as an excellent model to study mechanisms of activation of TOR and reinitiation events.
Nuclear export of mRNAs as ribonucleoproteic complexes via the Tap/p15 or CRM1 exportin pathways is widely studied in yeast and in metazoan. In plants, however, this crucial step in cell biology and in translation regulation remains almost unknown. We are focusing on deciphering the nuclear export mechanisms of plant and phytoviral mRNAs using CaMV and its spliced and unspliced 35S RNAs as model system.

Projects

Target of rapamycin, TOR, in translation initiation and reinitiation control in plants

Project manager: Lyubov RYABOVA

Rapid modulation in production of regulatory proteins can be achieved at the translation level using a multitude of specific mRNAs. uORFs located within the leaders of many mRNAs act as prevalent translation repressors that, in plants, are under control of TOR—a central controller of growth. Translation of uORF-containing mRNAs depends on a reinitiation mechanism that is far from elucidation in eukaryotes. Here we aim at investigating uORF-responsive translation (re)initiation mechanisms and their control by TOR using the shoot apical meristem as a model. In mammals, TOR controls translation efficiency by attenuating the repressive effect of eIF4E-binding proteins (4E-BPs) on cap-dependent translation initiation, while its role in plant cap-dependent translation initiation remains to be clarified. We are aiming to further investigate the role of TOR in plant translation control.

Funding—ANR ReinitiaTOR 2018

Members

Selected publications

  • RYABOVA L., ROBAGLIA C. and MEYER C.

    Target of Rapamycin kinase: central regulatory hub for plant growth and metabolism.

    Journal of Experimental Botany, 6, 2019.

  • SHCHEPETILNIKOV M. and RYABOVA L.

    Recent Discoveries on the Role of TOR (Target of Rapamycin) Signaling in Translation in Plants

    Plant Physiology, 176(2):1095–1105, 2018. | DOI : 10.1104/pp.17.01243DOI logo

  • SHCHEPETILNIKOV M., MAKARIAN J., SROUR O., GELDREICH A., YANG Z., CHICHER J., HAMMANN P. and RYABOVA L.

    GTPase ROP2 binds and promotes activation of target of rapamycin, TOR, in response to auxin

    EMBO Journal, 36:886-903, 2017. | DOI : 10.15252/embj.201694816DOI logo

  • GELDREICH A., HAAS G., KUBINA J., BOUTON C., TANGUY M., ERHARDT M., KELLER M., RYABOVA L. and DIMITROVA M.

    Formation of large viroplasms and virulence of Cauliflower mosaic virus in turnip plants depend on the N-terminal EKI sequence of viral protein TAV

    PLoS ONE, 12(12):e0189062, 2017. | DOI : 10.1371/ journal.pone.0189062DOI logo

  • SHCHEPETILNIKOV M., DIMITROVA M., MANCERA-MARTINEZ E., GELDREICH A. and RYABOVA L.

    TOR and S6K1 promote translation reinitiation of uORF-containing mRNAs via phosphorylation of eIF3h.

    EMBO Journal, 32(8):1087-1102, 2013. | DOI : 10.1038/emboj.2013.61DOI logo