We have been exploring how one signaling pathway – the TOR kinase pathway – promotes growth in Drosophila. TOR activity couples dietary nutrition to cell, tissue and body growth in larvae. Using this model system we made two discoveries:
1) We showed that tRNA synthesis is a key target of TOR in the control of mRNA translation and growth in vivo (Marshall et al 2012). We showed TOR works by inhibiting the Pol III repressor, Maf1. Moreover, we found that knockdown of Maf1 could drive tissue and body growth (Rideout et al 2012).
2) We made the striking discovery that simply increasing the synthesis of a single tRNA (the initiator, tRNAiMet) can promote mRNA translation, and accelerate body growth and development in Drosophila (Rideout et al 2012).
The translational control of gene expression is important throughout animal life – from regulating growth and form in the embryo to later effects on stress, memory and aging in adults. Most studies that investigate these effects focus on the contribution of mRNA binding proteins and translation initiation factors. Our findings suggest the intriguing model that simply increasing tRNA levels can drive translation, thus providing another layer of control on these varied biological functions.
We are currently addressing several questions raised by our work:
- How does TOR control Maf1 and tRNA synthesis?
- Do other growth signaling pathways work by increasing tRNA synthesis?
- How does an increase in tRNA levels influence mRNA translation?
- What are the mechanisms that link elevated tRNAs to enhanced tissue and body growth?
- Lastly, might tRNA synthesis also play in role in mediating other cellular and organismal functions of TOR signaling?