Recent studies have revealed heterogeneous ribosomes exist in different tissues and translate different mRNAs. Heterogenous ribosomes can be characterized by their rRNA type, rRNA modification, RP composition, etc. In Drosophila, there are ribosomal proteins which have multiple paralogs, such as RpS5A and RpS5B, that show different expression pattern through development, but nothing is known about their specialized function.
Our preliminary data show that loss of RpS5B induces female sterility caused by egg chamber development arrest around stage 7.
To study the function of RpS5B in germline development, we are currently working to:
- Test redundancy in RpS5A and RpS5B
- Characterize genes which shows changed translation in the mutant
- Regulation of signaling pathways in germline development
Most research on ribosome biogenesis and protein synthesis uses yeast or mammalian cell lines, but this work provides only an averaged picture of these fundamental processes; it can't reveal dynamic differences among individual cells in vivo.
Strikingly, emerging data show that the dynamic regulation of rRNA transcription and ribosome biogenesis directly impacts the fate and function of different cell types across species.
Unfortunately, robust and genetically tractable models for studying the differential regulation of ribosome formation have not been available until recently. We overcame this obstacle by identifying a Drosophila RNA Polymerase I (Pol I) regulatory complex that resembles the human SL1 complex. This complex regulates the proliferation and growth of germline stem cells (GSCs). Our published work and new preliminary data indicate that modulation of Pol I activity influences cell fate and function in several different tissues.
A critical question now becomes how different types of cells establish different rates of rRNA transcription and ribosome assembly. Our discovery of the Drosophila SL1 complex provides a unique opportunity to identify and characterize mechanisms that modulate rRNA transcription and ribosome biogenesis in different cell types in vivo. We have also begun to characterize a number of enzymes, including NO66 and MINA, which may regulate ribosome biogenesis and function.
To explore how and what regulates rRNA transcription, we are seeking to:
- Reconstitute rRNA transcription reporter in mammalian cells
- Genome-wide screening to find positive and negative regulator of rRNA transcription
- rRNA transcription change in various stress condition