Space radiation and microgravity are recognized as primary and inevitable risk factors for humans traveling in space, but the reports regarding their synergistic effects remain inconclusive and vary across studies due to differences in the environmental conditions and intrinsic biological sensitivity. Thus, we studied the synergistic effects on transcriptional changes in the global genome and DNA damage response (DDR) by using dys-1 mutant and ced-1 mutant of C. elegans, which respectively presented microgravity-insensitivity and radiosensitivity when exposure to spaceflight condition (SF) and space radiation (SR). The dys-1 mutation induced similar transcriptional changes under both conditions, including the transcriptional distribution and function of altered genes. The majority of alterations were related to metabolic shift under both conditions, including transmembrane transport, lipid metabolic processes and proteolysis. Under SF and SR conditions, 12/14 and 10/13 altered pathways, respectively, were both grouped in the metabolism category. Out of the 778 genes involved in DDR, except eya-1 and ceh-34, 28 altered genes in dys-1 mutant showed no predicted protein interactions, or anti-correlated miRNAs during spaceflight. The ced-1 mutation induced similar changes under SF and SR; however, these effects were stronger than those of the dys-1 mutant. The additional genes identified were related to phosphorous/phosphate metabolic processes and growth rather than, metabolism, especially for environmental information processing under SR. Although the DDR profiles were significantly changed under both conditions, the ced-1 mutation favored DNA repair under SF and apoptosis under SR. Notably, 37 miRNAs were predicted to be involved in the DDR. Our study indicates that, the dys-1 mutation reduced the transcriptional response to SF, and the ced-1 mutation increased the response to SR, when compared with the wild type C. elegans. Although some effects were due to radiosensitivity, microgravity, depending on the dystrophin, exerts predominant effects on transcription in C. elegans during short-duration spaceflight.

中文翻译：

---

在神舟八号飞行中，线虫的DNA损伤反应受到重力感应和放射敏感性的影响。

空间辐射和微重力被认为是人类在太空旅行的主要和不可避免的危险因素，但是由于环境条件和内在生物学敏感性的差异，有关其协同作用的报告仍然没有定论，并且在各个研究中有所不同。因此，我们通过使用秀丽隐杆线虫的dys-1突变体和ced-1突变体研究了对全球基因组转录变化和DNA损伤反应（DDR）的协同效应，当它们暴露于太空条件下时分别表现出微重力不敏感性和放射敏感性。 （SF）和空间辐射（SR）。dys-1突变在两种条件下均诱导了相似的转录变化，包括转录分布和基因改变的功能。在两种情况下，大多数变化与代谢转移有关，包括跨膜转运，脂质代谢过程和蛋白水解。在SF和SR条件下，分别将12/14和10/13改变的途径都归为新陈代谢类别。在DDR涉及的778个基因中，除了eya-1和ceh-34之外，dys-1突变体中的28个改变的基因在太空飞行中均未显示出预期的蛋白质相互作用或抗相关的miRNA。ced-1突变在SF和SR下引起相似的变化。但是，这些作用比dys-1突变体的作用更强。鉴定出的其他基因与磷/磷酸盐的代谢过程和生长有关，而不是与代谢有关，特别是与SR下的环境信息处理有关。尽管在两种情况下DDR配置文件均发生了显着变化，ced-1突变有利于SF下的DNA修复和SR下的细胞凋亡。值得注意的是，预计有37个miRNA参与DDR。我们的研究表明，与野生型秀丽隐杆线虫相比，dys-1突变减少了对SF的转录反应，而ced-1突变增加了对SR的反应。尽管某些影响是由于放射敏感性引起的，但微重力（取决于抗肌萎缩蛋白）在短时航天中对秀丽隐杆线虫的转录起主要作用。