Muscle-specific knockdown of TIF-IA leads to reduced body size (centre larvae). This is partially rescued by inhibition of Imp-L2, an insulin inhibitor – see Ghosh et al, 2014
Ribosome synthesis is one of the chief metabolic efforts in a cell and is a key determinant of protein synthesis capacity and growth. In eukaryotes, ribosome synthesis requires three different RNA polymerase (Pol) complexes to synthesize ribosome components: Pol I to synthesize ribosomal RNA, Pol II to synthesize ribosomal protein (RP) mRNA, and Pol III to synthesize 5S RNA . Upward of 6000 ribosomes are produced per minute in growing cells, with Pol I activity accounting for 60% of all nuclear transcription and RP mRNA synthesis accounting for 50% of all Pol II transcription.
Knockdown of TIF-IA by RNAi (GFP cells) reduces fat body cell size – See Grewal et al 2007
We have been looking at how regulation of ribosome synthesis controls cell, tissue and body growth. So far our work has focused on the nutrient-dependent TOR kinase pathway. We’ve shown that TOR can control rRNA synthesis via the Pol I transcription factor TIF-IA, and that this regulation is important for growth (Grewal et al). We’ve also identified how TOR can control expression of ribosome biogenesis genes (Killip and Grewal; Li et al).
Some questions we’re asking now:
- Do other growth signaling pathways function by controlling ribosome synthesis and protein synthesis?
- Is regulation of ribosome synthesis important for stress responses in larvae?
- Does regulation of ribosome synthesis contribute to protein synthesis control in adults and regulation of processes such as stress tolerance, infection and aging?
The Grewal Lab 