The DEAD-box RNA helicase eIF4A is a crucial factor for stem-cell activity and reproduction of the parasite Schistosoma mansoni.

INTRODUCTION: The parasite Schistosoma mansoni has a unique reproductive biology, because female maturation depends on constant pairing with a male. Paired females produce each up to 300 eggs per day, which are the pathogenic factors of schistosomiasis, a neglected tropical disease that affects > 240 million people worldwide. Due to the importance of egg production for life-cycle maintenance and pathology, molecular mechanisms controlling schistosome reproduction are in the focus of research. Among the candidates involved in regulating the reproductive biology of this parasite are DEAD-box RNA helicases. These enzymes are associated with various cellular processes, including ribosome biogenesis and post-transcriptional regulation. In platyhelminths, helicases are largely unexplored. One member of the DEAD-box helicase family is the eukaryotic translation initiation factor 4A (eIF4A), which unwinds stable RNA structures in the 5'-untranslated region of selected mRNAs.

OBJECTIVES: We functionally characterized two eIF4A isoforms of S. mansoni (SmeIF4A-a and SmeIF4A-b), which are potentially involved in translation initiation like their human orthologs, to evaluate their importance for parasite vitality and reproduction.

METHODOLOGIES/FINDINGS: Transcripts of both SmeIF4A isoforms were localized in female ovaries as shown by whole mount in situ hybridization. RNA-interference (RNAi) experiments revealed a decisive role of SmeIF4A-a in gonad maintenance and egg production. Stem-cell proliferation assays and confocal laser scanning microscopy uncovered the loss of proliferation activity in germinal and somatic stem cells after Smeif4a-a RNAi. No distinct function was found for SmeIF4A-b.

CONCLUSION: Our results suggest that SmeIF4A-a is a key factor in stem-cell proliferation and gonad maintenance, and thus also in egg production.