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

TL;DR

This study identifies a crucial role for the eIF4A protein in the reproduction and stem-cell activity of the Schistosoma mansoni parasite.

Contribution

The study reveals that SmeIF4A-a is essential for stem-cell proliferation and egg production in Schistosoma mansoni.

Findings

SmeIF4A-a is vital for gonad maintenance and egg production in Schistosoma mansoni.

RNAi of SmeIF4A-a leads to loss of proliferation in germinal and somatic stem cells.

SmeIF4A-b does not show a distinct functional role in reproduction.

Abstract

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.

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.

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.

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

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