The origin of pattern through control of mRNA translation and stability

Translational control is an essential mechanism of gene control utilized throughout development, yet the molecular mechanisms underlying translational activation and repression are poorly understood. In C. elegans , early polarity cues control the expression of genes that pattern the anterior-posterior embryonic axis. We are investigating the post-transcriptional control mechanisms that target expression of the caudal -like gene pal-1 to posterior blastomeres in 4-cell and older embryos. Through genetic studies we have identified proteins required for repression of translation and, importantly for developmental processes, spatially and temporally controlled de-repression. In particular, components of the conserved RNA induced silencing complex (RISC) appear to be required for efficient translational repression. C. elegans is a terrific system for molecular genetic analysis development control pathways, but its potential for traditional biochemical analysis has not been fully exploited. The accessibility of the germline to direct experimental manipulation via microinjection has encouraged us to develop complementary in vitro assays to investigate the activity of these proteins. Our analysis to date provides strong support for post-initiation repression, a mechanism conducive to a rapid transition to productive protein synthesis, which is critical during the rapid phase of early development. Current efforts are focused on elucidating the mechanism(s) that limits accumulation of mature protein from polyribosome associated mRNAs.

Participating Lab Members:

Name Research
Jacqueline (Jack) M. BrooksTranslational regulatory mechanisms of maternal mRNAs in the C. elegans germline.
Edgar (Ned) ButtnerGermline biology of C. elegans lis-1
Erica FarberGermline biology of C. elegans lis-1
Aleksandra (Ola) Gil-KrzewskaGermline biology of C. elegans lis-1
Nikki PatelGermline biology of C. elegans lis-1
Anandita (Nina) RajpurohitGermline biology of C. elegans lis-1