| RNA regulation is crucial for many aspects of metazoan development including regulation of stem cells and synaptic plasticity. Particularly, in the germ line of virtually all organisms examined, conserved RNA regulators play a variety of prominent roles. This work focuses on the molecular mechanisms of the mitosis/meiosis decision in the C. elegans germ line by the conserved cPAP protein, GLD-2, and the PUF protein, FBF.; To investigate the molecular switch controlling the mitosis/meiosis decision, I first set out to identify target mRNAs of the GLD-2 cPAP using a candidate gene approach. I found that GLD-2 directly activates gld-1 mRNA and this activation identifies a positive regulatory step to drive germ cells robustly into meiotic cell cycle. Interestingly, that same RNA was previously shown to be a direct target of FBF repression.; I next explored the possible mechanisms for FBF repression and the switch to GLD-2 activation in collaboration with other members of Kimble and Wickens labs. We found that FBF is capable of recruiting the yeast Ccr-4-Pop2-Not complex to promote deadenylation of a target RNA. In addition, the C. elegans Pop2 homolog affects GLD-1 expression. Surprisingly, FBF also interacts with GLD-2 either directly or indirectly, with GLD-3, a Bicaudal-C RNA binding protein serving as a bridge. These results, together with results from genetic tests done previously, place FBF in the GLD-2 pathway to promote meiotic entry. Therefore, FBF appears to be a key component of the switch from proliferation to differentiation. The switch between FBF repression and GLD-2 activation provides a paradigm for the binary control of key target mRNAs during development. |
