Abstract
BackgroundOvercoming spaceflight-induced (patho)physiologic adaptations is a major challenge preventing long-term deep space exploration. RNA interference (RNAi) has emerged as a promising therapeutic for combating diseases on Earth; however the efficacy of RNAi in space is currently unknown.Methods Caenorhabditis elegans were prepared in liquid media on Earth using standard techniques and treated acutely with RNAi or a vector control upon arrival in Low Earth Orbit. After culturing during 4 and 8 d spaceflight, experiments were stopped by freezing at −80°C until analysis by mRNA and microRNA array chips, microscopy and Western blot on return to Earth. Ground controls (GC) on Earth were simultaneously grown under identical conditions.ResultsAfter 8 d spaceflight, mRNA expression levels of components of the RNAi machinery were not different from that in GC (e.g., Dicer, Argonaute, Piwi; P>0.05). The expression of 228 microRNAs, of the 232 analysed, were also unaffected during 4 and 8 d spaceflight (P>0.05). In spaceflight, RNAi against green fluorescent protein (gfp) reduced chromosomal gfp expression in gonad tissue, which was not different from GC. RNAi against rbx-1 also induced abnormal chromosome segregation in the gonad during spaceflight as on Earth. Finally, culture in RNAi against lysosomal cathepsins prevented degradation of the muscle-specific α-actin protein in both spaceflight and GC conditions.ConclusionsTreatment with RNAi works as effectively in the space environment as on Earth within multiple tissues, suggesting RNAi may provide an effective tool for combating spaceflight-induced pathologies aboard future long-duration space missions. Furthermore, this is the first demonstration that RNAi can be utilised to block muscle protein degradation, both on Earth and in space.
Highlights
The RNA interference (RNAi) machinery regulates posttranscriptional gene expression by using small (,20 nucleotide long) non-coding double-stranded RNA molecules, in combination with nuclease-containing argonaute complexes, to sequence- silence target mRNAs
We report for the first time the stable expression of microRNAs and mRNA of genes encoding for components of the RNAi machinery during spaceflight
Expression of RNAi machinery and microRNAs are normal after spaceflight
Summary
The RNA interference (RNAi) machinery regulates posttranscriptional gene expression by using small (,20 nucleotide long) non-coding double-stranded RNA (dsRNA) molecules, in combination with nuclease-containing argonaute complexes, to sequence- silence target mRNAs. Preventing attainment of this goal is the frequent occurrence of various (patho)physiologic adaptations during spaceflight, which may be detrimental for crew health and mission performance. Decreases in skeletal muscle mass occur during spaceflight [4,5,6] to levels which are sufficient to impair contractile function [4] and rehabilitation [7]. In order to minimise the inherent risks associated with embarking on longterm deep space explorations, effective countermeasures to these (mal)adaptations must be developed. Overcoming spaceflight-induced (patho)physiologic adaptations is a major challenge preventing long-term deep space exploration. RNA interference (RNAi) has emerged as a promising therapeutic for combating diseases on Earth; the efficacy of RNAi in space is currently unknown
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