Telonis-Scott Marina, Clemson Allannah S, Johnson Travis K, Sgrò Carla M
School of Biological Sciences, Monash University, Clayton, Vic., 3800, Australia.
Mol Ecol. 2014 Dec;23(24):6135-51. doi: 10.1111/mec.13000. Epub 2014 Dec 4.
The cellular stress response has long been the primary model for studying the molecular basis of thermal adaptation, yet the link between gene expression, RNA metabolism and physiological responses to thermal stress remains largely unexplored. We address this by comparing the transcriptional and physiological responses of three geographically distinct populations of Drosophila melanogaster from eastern Australia in response to, and recovery from, a severe heat stress with and without a prestress hardening treatment. We focus on starvin (stv), recently identified as an important thermally responsive gene. Intriguingly, stv encodes seven transcripts from alternative transcription sites and alternative splicing, yet appears to be rapidly heat inducible. First, we show genetic differences in upper thermal limits of the populations tested. We then demonstrate that the stv locus does not ubiquitously respond to thermal stress but is expressed as three distinct thermal and temporal RNA phenotypes (isoforms). The shorter transcript isoforms are rapidly upregulated under stress in all populations and show similar molecular signatures to heat-shock proteins. Multiple stress exposures seem to generate a reserve of pre-mRNAs, effectively 'priming' the cells for subsequent stress. Remarkably, we demonstrate a bypass in the splicing blockade in these isoforms, suggesting an essential role for these transcripts under heat stress. Temporal profiles for the weakly heat responsive stv isoform subset show opposing patterns in the two most divergent populations. Innate and induced transcriptome responses to hyperthermia are complex, and warrant moving beyond gene-level analyses.
细胞应激反应长期以来一直是研究热适应分子基础的主要模型，但基因表达、RNA代谢与热应激生理反应之间的联系在很大程度上仍未得到探索。我们通过比较来自澳大利亚东部的三个地理上不同的黑腹果蝇种群在有或没有预应激硬化处理的情况下对严重热应激的反应及恢复过程中的转录和生理反应来解决这个问题。我们关注最近被鉴定为重要热响应基因的starvin（stv）。有趣的是，stv从可变转录位点和可变剪接编码七种转录本，但似乎能被快速热诱导。首先，我们展示了所测试种群的热上限存在遗传差异。然后我们证明stv基因座并非对热应激普遍做出反应，而是表现为三种不同的热和时间RNA表型（异构体）。较短的转录本异构体在所有种群的应激状态下均迅速上调，并且显示出与热休克蛋白相似的分子特征。多次应激暴露似乎会产生前体mRNA储备，有效地“启动”细胞以应对后续应激。值得注意的是，我们证明了这些异构体中剪接阻断的旁路，表明这些转录本在热应激下具有重要作用。在两个差异最大的种群中，对热应激反应较弱的stv异构体子集的时间分布呈现出相反的模式。对热疗的固有和诱导转录组反应很复杂，需要超越基因水平的分析。
