Post-Transcriptional Dynamics is Involved in Rapid Adaptation to Hypergravity in Jurkat T Cells

The transcriptome of human immune cells rapidly reacts to altered gravity in a highly dynamic way. We could show in previous experiments that transcriptional patterns show profound adaption after seconds to minutes of altered gravity. To gain further insight into these transcriptional alteration and adaption dynamics, we conducted a highly standardized RNA-Seq experiment with human Jurkat T cells exposed to 9xg hypergravity for 3 and 15 min, respectively. We investigated the frequency with which individual exons were used during transcription and discovered that differential exon usage broadly appeared after 3 min and became less pronounced after 15 min. Additionally, we observed a shift in the transcript pool from coding towards non-coding transcripts. Thus, adaption of gravity-sensitive differentially expressed genes followed a dynamic transcriptional rebound effect. The general dynamics were compatible with previous studies on the transcriptional effects of short hypergravity on human immune cells and suggest that initial up-regulatory changes mostly result from increased elongation rates. The shift correlated with a general downregulation of the affected genes. All chromosome bands carried homogenous numbers of gravity-sensitive genes but showed a specific tendency towards up- or downregulation. Altered gravity affected transcriptional regulation throughout the entire genome, whereby the direction of differential expression was strongly dependent on the structural location in the genome. A correlation analysis with potential mediators of the early transcriptional response identified a link between initially upregulated genes with certain transcription factors. Based on these findings, we have been able to further develop our model of the transcriptional response to altered gravity.

Automated summary

The transcriptome of human immune cells responds rapidly to altered gravity in a highly dynamic way, with profound adaptation seen in transcriptional patterns within seconds to minutes. In this study, human Jurkat T cells were exposed to 9xg hypergravity for 3 and 15 minutes, and RNA-Seq analysis revealed differential exon usage after 3 minutes, which became less pronounced after 15 minutes. Additionally, a shift in the transcript pool from coding to non-coding transcripts was observed. These findings suggest that gravity-sensitive differentially expressed genes follow a dynamic transcriptional rebound effect, with initial up-regulatory changes resulting from increased elongation rates. The direction of differential expression depended on the structural location in the genome. Furthermore, a correlation analysis identified a link between initially upregulated genes and specific transcription factors, providing further insight into the transcriptional response to altered gravity.