Control of the sperm–oocyte switch in Caenorhabditis elegans hermaphrodites by the fem-3 3′ untranslated region

Abstract

IN the Caenorhabditis elegans hermaphrodite germ line, sperm and then oocytes are made from a common pool of germ-cell precursors. The decision to differentiate as a sperm or an oocyte is regulated by the sex-determining gene,fem-3. Expression of fem-3 in the hermaphrodite germ line directs spermatogenesis and must be negatively regulated to allow the switch to oogenesis^1,2. In adult hermaphrodites (which are producing oocytes), mostfem-3 RNA is found in the germ line³, consistent with both the requirement for fem-3 in hermaphrodite spermatogenesis and the maternal effects of fem-3 on embryonic sex determination^1,2Whereas loss-of-function mutants in fem-3 produce only oocytes, hermaphrodites carrying any of nine fem-3 gain-of-function (gf) mutations make none; instead sperm are produced continuously and in vast excess over wild-type amounts¹Genetic analyses suggest that fem-3(gf) mutations have escaped a negative control required for the switch to oogenesis¹. Here we report that all nine fem-3(gf) mutants carry sequence alterations in the fem-3 3′ untranslated region (3′ UTR). There is no increase in the steady-state level of fem-3(gf) RNA over wild-type, but there is an increase in the polyadenylation of fem-3(gf) RNA that is coincident with the unregulated fem-3 sactivity. Results of a titration experiment support the hypothesis that a regulatory factor may bind the fem-3 3′ UTR. We speculate that fem-3 RNA is regulated through its 3′ UTR by binding a factor that inhibits translation, and discuss the idea that this control may be part of a more general regulation of maternal RNAs.