Despite the importance of the nuclear envelope in the cell and its implication in a wide variety of diseases, very little is known about the function of individual components that make up this organelle. A recent proteomic study in mammalian cells (Schirmer et al, 2003) identified 67 new integral nuclear membrane components on top of the approximately a dozen components that were previously known. Our BLAST searches identified 51 potential new nuclear envelope components conserved in C. elegans. To gain some new insights into the nuclear envelope, we are using C. elegans as a model system and employing a reverse genetic approach using RNAi against 51 newly identified, evolutionarily conserved components of the nuclear envelope. We are screening progeny of dsRNA-injected animals for post-embryonic defects in nuclear migration and anchorage similar to null phenotypes in
unc-83,
unc-84, and
anc-1. We are also screening for synthetic lethality with
emr-1(
gk119). Mutations in emerin have been shown to lead to Emery-Dreifuss muscular dystrophy in human, but are silent in worms (Gruenbaum et al, 2002). We confirmed that
lem-2(RNAi);
emr-1(
gk119) animals are synthetic lethal, as previously shown (Liu et al, 2003). Finally, we are cloning the 51 new potential nuclear envelope proteins into GFP fusion vectors under control of the ubiquitous
npp-1 promoter (kind gift of A. Schetter and K. Kemphues) to confirm their predicted localization to the nuclear envelope.