The putative DEAD-box helicase LAF-1 and its role in Caenorhabditis elegans sex determination

Wild-type Caenorhabditis elegans worms develop as either males or hermaphrodites, and sexual cell fate decisions are controlled by a complex network of genes. A central regulator in this network, TRA-2, promotes female development in both the soma and germ line. Spermatogenesis in the hermaphrodite germ line requires repression of tra-2 expression at the level of translation. Export of tra-2 mRNA from the nucleus is also regulated, so that tra-2 mRNA exits via a CRM-1-mediated pathway, rather than the bulk mRNA export pathway mediated by NXF-1. Laf-1 is critical for both embryonic development and sex determination. Laf-1 is thought to promote male cell fates by negatively regulating expression of tra-2 in both hermaphrodites and males. I cloned laf-1 and established that it encodes a putative DEAD-box RNA helicase. Three sequenced laf-1 mutations are missense alleles affecting a small region of the protein in or near helicase motif III. Laf-1(RNAi) mimics the laf-1 mutations in feminization and embryonic lethality. Laf-1 mRNA is expressed in both males and hermaphrodites and in both the germ line and soma of hermaphrodites. It is expressed at all developmental stages and is most abundant in embryos. LAF-1 is predominantly, if not exclusively, cytoplasmic and colocalizes with PGL-1 in P granules of germ line precursor cells. I found that the abundance of TRA-2 protein is modestly elevated in laf-1/+ females, supporting the model that LAF-1 negatively regulates expression of TRA-2. LAF-1 is a member of a conserved family of helicases that includes human DDX3, S. cerevisiae Ded1p, and Drosophila Vasa. LAF-1-related proteins function in germ line development and usually regulate translation or nuclear export of mRNAs. I discuss potential functions of LAF-1 as a helicase and its roles in sex determination.