Hc-fau, a novel gene regulating diapause in the nematode parasite Haemonchus contortus

Diapause induced in the early fourth stage of Haemonchus contortus is a strategy to adapt this nematode to hostile environmental conditions. In this study, we identified a new gene, Hc-fau, a homologue of human fau and Caenorhabditis elegans Ce-rps30. Hc-fau encodes two proteins through alternative RNA splicing, Hc-FAUA and Hc-FAUB, consisting of 130 and 107 amino acids, respectively. Hc-FAU possesses a diverged ubiquitin-like (UBiL) protein domain and a conserved ribosome protein S30 domain. The protein is ubiquitously expressed, except in the gonad. However Hc-fau transcripts decrease significantly in diapausing L4s of H. contortus. In C elegans, knockdown of Ce-rps30 confers an extended lifespan, increased lipid storage in the intestine and shortened body length. These morphological characteristics are comparable with dauer larvae of C elegans, in which the gonad is condensed considerably. In contrast, a shortened lifespan is observed in C elegans over-expressing Hc-faua, and especially Hc-faub, with hatching failure detected. The genes of insulin/IGF-1 signalling (IIS), TGF-beta, cGMP, dafachronic acid (DA), apoptosis (AP) and fatty acids (FA) metabolism are all down-regulated in Ce-rps3ORNAi (RNA interference) worms, except for akt-1 and daf-16. However, daf-16 up-regulation is inconsistent with its target gene down-regulation and the result from a heat stress assay in these worms. Daf-16 RNAi conducted in Ce-rps30 (tm6034/nt1) mutants failed to rescue the worms. The S30 domain stays in the nucleus, while UBiL accumulates in the cytoplasm. Compared with Hc-FAUA, results of UBiL domain and S30 domain overexpression indicate synergism between UBiL and S30 in regulating lifespan and reproduction. These results suggest the potential functions of Hc-fau in regulating larval diapause in H. contortus. (C) 2014 Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc.