ReinitiaTOR

Growth and regeneration in all organisms depends on a proper balance between stem cell division and differentiation. Despite extensive study of the transcriptional and epigenetic networks that control stem cell populations, mechanisms of post-transcriptional regulation in the stem cell niche remain unknown. 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 (target of rapamycin)—a central controller of growth. 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, suggesting a TOR-dependent function in controlling protein levels of stem cell regulators that will be tested in this project. We predict that TOR by de-repressing translation of pre-existing mRNAs of key meristematic factors downstream of auxin would allow rapid modulation of the stem cell niche activity during development, a key hypothesis that will be tested in this project. The main objectives of the project are four-fold : 1. Screening for meristematic mRNAs that are under translation repression by uORFs, and determining the role of TOR in activation of their translation 2. Deciphering the mechanism of eIF3h function in TOR-responsive reinitiation of translation 3. Understanding the impact of uORF suppressors on SAM size, structure, growth and organogenesis in different TOR contrasting conditions 4. Analyzing the TOR-dependent function of auxin in regulation of stem cell niche regulator translation We expect to discover and analyse meristem-related genes with translatable uORFs under post-transcriptional control of the auxin-TOR signaling axis. This project is expected to provide fundamental knowledge on emerging translation reinitiation mechanisms in plants that would help to understand these translation strategies in animals. Indeed, given the high conservation of TOR, understanding how TOR impacts stem cell development would provide us with potential tools to manipulate stem cell niche activity in plant and also in animal cells. In humans, this could prove to be essential for fighting tumorigenesis, and, in plants, recent data have shown that regulation of stem cell niche activity has a strong potential for the manipulation of yield.