TOR signalling control in plant translation

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 such as protein synthesis, plant growth and organogenesis. A central signaling molecule that correlates growth with nutrients and energy sufficiency is the target of rapamycin (TOR). TOR is a major controller of translation initiation in mammals and yeast.
In eukaryotes, protein production is limited by upstream open reading frames (uORFs) located within the 5’UTRs of about 30% of eukaryotic mRNAs encoding highly potent regulatory proteins (e.g. growth factors, protein kinases, and transcription factors). Translation of uORF-containing mRNAs (uORF-mRNAs) depends on a reinitiation mechanism, where ribosomes terminating translation of a uORF resume scanning and reinitiate at an ORF further downstream on the same mRNA. Although mechanisms of translation reinitiation are not well understood, subunit h of eukaryotic translation initiation factor 3 (eIF3), if phosphorylated by the TOR signalling pathway, was shown to be a critical essential reinitiation factor.
In plants, we have established that TOR perceives growth hormone auxin through a small GTPase ROP2 that directly binds and activates TOR and thereby promotes translation reinitiation and plant growth. Currently, the auxin–ROP2–TOR signaling axis represents the most well studied example of upstream TOR regulation.
Our team works on novel TOR upstream effectors and downstream targets studying their role in reinitiation and cap-dependent initiation of translation in plants. Cauliflower mosaic virus (CaMV) employs an unique strategy to translate viral polycistronic 35S RNA by using the reinitiation mechanism. To understand mechanisms of reinitiation after uORF translation, we study how a CaMV translational transactivator/ viroplasmin (TAV) overcomes cellular barriers to reinitiation after long ORF translation.

Our research programs are supported by international (Marie-Curie fellowships) and national (ANR) programmes.

Projects

The TOR signaling pathway in translation reinitiation in plants

Translation is a critical step in controlling gene activity; upstream ORFs (uORFs) located within the leaders of many mRNAs act as prevalent translation repressors that, in plants, are under control of TOR. Plant stem cell mRNAs are heavily enriched in uORFs, and we aim to study uORF-responsive translation mechanisms and their control by TOR in the shoot apical meristem—a specialized tissue containing a stem cell niche and responsible for building shoots. TOR is also controlled by the plant hormone auxin, and we are testing a TOR-dependent function in controlling protein levels of stem cell regulators. We continue studying upstream effectors of TOR as well as TOR downstream targets and reveal their functions in translation reinitiation; deciphering the mechanism of TOR-responsive reinitiation after short ORF translation and the role of the translation reinitiation factor h (eIF3h) and the 40S ribosomal protein S6 (eS6) in reinitiation after uORF translation.

The TOR signaling pathway in cap-dependent translation initiation in Arabidopsis

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 have identified eIF4E-binding proteins responsive to TOR that potentially able to fill this role in plants.This project aims to understand whether, and how, TOR controls the translation initiation process in plants through Arabidopsis 4E-BP-like proteins during cap dependent translation initiation in normal and stress conditions as well as to determine the functional significance of 4E-BP-like proteins. We are searching for candidate cellular mRNAs under the control of TOR and 4E-BP-like proteins using ribosomal profiling. This project aims to understand whether, and how, TOR controls the translation initiation process in plants through 4E-BP-like proteins.

Members

Selected publications

  • LUKHOVITSKAYA N. and RYABOVA L.

    Cauliflower mosaic virus transactivator protein (TAV) can suppress nonsense-mediated decay by targeting VARICOSE, a scaffold protein of the decapping complex.

    Scientific Reports, 7042, 2019. | DOI : 10.1038/s41598-019-43414-0DOI logo

  • 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

  • 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