Translational regulation is a key regulatory mechanism that controls protein levels during the development and homeostasis of essentially all organisms. Due to a general silencing of transcription in the germ line, translational regulation plays a central role and many RNA binding proteins have been identified that regulate distinct steps during germline development. An emerging theme is that individual RNA binding proteins appear to exert their effect on development through the coordinate control of batteries of RNA targets. However, to date a comprehensive understanding of how a single RNA binding protein coordinately regulates germline development remains elusive.

Our lab is interested in elucidating the genetic and molecular basis through which a particular RNA binding protein governs multiple mRNA targets in order to control many distinct cellular processes during C. elegans germline development. We focus on GLD-1, a Maxi-KH domain containing RNA binding protein that acts during essentially all stages of C. elegans germline development from germline stem cells to mature gametes. Interestingly, genetic elimination of gld-1 causes a germline tumor, suggesting that mis-regulation of certain mRNA targets leads to tumor formation.

We have demonstrated that GLD-1 represses the translation of mRNA targets and have recently identified over 100 GLD-1 mRNA targets with microarray studies. Present projects arise from this work and include (i) understanding the importance of coordinated control of mRNA targets by GLD-1 during C. elegans germline development, (ii) identification of the sequence(s) and/or structure(s) that distinguishes target from non-target mRNAs, (iii) determining if translational repression of mRNA targets occurs prior to or after translation initiation, (iv) investigating to resolve whether microRNAs collaborate with proteins such as GLD-1 during translational repression of mRNA targets, and (v) determining mRNA targets whose mis-regulation leads to the germline tumor in the absence of GLD-1.

Fig. 1. Spatial pattern of GLD-1 and one of the GLD-1 targets, RME-2. Schematic representation of the adult hermaphrodite germline and qualitative depiction of GLD-1 protein levels (solid green line), protein level (long-dashed red line) and mRNA level (short-dashed line) for a number of GLD-1 targets are shown in the upper panel. Lower panel shows a wild-type adult hermaphrodite gonad that is stained for DNA (DAPI, blue), GLD-1 (green), and one of the GLD-1 targets, RME-2 (red).