RNAi-based screen to identify gene products required for HOW activity in controlling tissue differentiation
Volk's lab

RNA-binding proteins regulate protein expression levels by affecting various aspects of RNA metabolism, including pre-mRNA splicing, mRNA stability, nuclear export, and association with the translational machinery. A single RNA-binding protein may bind to an array of target mRNAs to regulate various differentiation processes. Proteins of the STAR family (Signal Trunsduction and RNA regulation), including Drosophila HOW, are conserved in evolution, and function to regulate key differentiation processes in many species.
Drosophila how gene produces two alternatively spliced protein isoforms, HOW(L) and HOW(S). The relative levels of HOW(L)/HOW(S) define the state of differentiation of different cell types including: glia, tendon and heart cells (Nabel-Rosen et al.,1999, 2002).
Despite the critical contribution of STAR proteins to an array of differentiation processes in various species the molecular mechanism by which they exert their activity on mRNAs remains to be elucidated.
Here we wish to address two main questions regarding HOW activity: What is the identity of the molecular pathways regulating HOW(L) activity in inducing mRNA degradation in the cells.
What are the gene products required for RNA stabilization and splicing exerted by HOW(S).
To address these questions we have implicated a whole genome dsRNA-based screen to identify genes required for HOW-induced degradation of mRNAs. Several genes were recovered and are currently characterized.
Following characterization of HOW function in the induction of apoptosis of the midline glial cells in the embryonic CNS, we have now found that the steroid hormone Ecdyson regulates the levels of HOW protein in the midline glial cells, and that this is an important step towards the death of those cells.