Multi-modal regulation of C. elegans hermaphrodite spermatogenesis by the GLD-1-FOG-2 complex

Dev Biol. 2019 Feb 15;446(2):193-205. doi: 10.1016/j.ydbio.2018.11.024. Epub 2018 Dec 30.


Proper germ cell sex determination in Caenorhabditis nematodes requires a network of RNA-binding proteins (RBPs) and their target mRNAs. In some species, changes in this network enabled limited XX spermatogenesis, and thus self-fertility. In C. elegans, one of these selfing species, the global sex-determining gene tra-2 is regulated in germ cells by a conserved RBP, GLD-1, via the 3' untranslated region (3'UTR) of its transcript. A C. elegans-specific GLD-1 cofactor, FOG-2, is also required for hermaphrodite sperm fate, but how it modifies GLD-1 function is unknown. Germline feminization in gld-1 and fog-2 null mutants has been interpreted as due to cell-autonomous elevation of TRA-2 translation. Consistent with the proposed role of FOG-2 in translational control, the abundance of nearly all GLD-1 target mRNAs (including tra-2) is unchanged in fog-2 mutants. Epitope tagging reveals abundant TRA-2 expression in somatic tissues, but an undetectably low level in wild-type germ cells. Loss of gld-1 function elevates germline TRA-2 expression to detectable levels, but loss of fog-2 function does not. A simple quantitative model of tra-2 activity constrained by these results can successfully sort genotypes into normal or feminized groups. Surprisingly, fog-2 and gld-1 activity enable the sperm fate even when GLD-1 cannot bind to the tra-2 3' UTR. This suggests the GLD-1-FOG-2 complex regulates uncharacterized sites within tra-2, or other mRNA targets. Finally, we quantify the RNA-binding capacities of dominant missense alleles of GLD-1 that act genetically as "hyper-repressors" of tra-2 activity. These variants bind RNA more weakly in vitro than does wild-type GLD-1. These results indicate that gld-1 and fog-2 regulate germline sex via multiple interactions, and that our understanding of the control and evolution of germ cell sex determination in the C. elegans hermaphrodite is far from complete.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Hermaphroditic Organisms / genetics*
  • Hermaphroditic Organisms / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Models, Genetic
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Mutation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • 3' Untranslated Regions
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • GLD-1 protein, C elegans
  • Membrane Proteins
  • Multiprotein Complexes
  • RNA, Messenger
  • Transcription Factors
  • fog-2 protein, C elegans
  • tra-2 protein, C elegans