School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
School of Computing Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
Proc Biol Sci. 2018 Sep 26;285(1887):20181681. doi: 10.1098/rspb.2018.1681.
Highly precise, yet flexible and responsive coordination of expression across groups of genes underpins the integrity of many vital functions. However, our understanding of gene regulatory networks (GRNs) is often hampered by the lack of experimentally tractable systems, by significant computational challenges derived from the large number of genes involved or from difficulties in the accurate identification and characterization of gene interactions. Here we used a tractable experimental system in which to study GRNs: the genes encoding the seminal fluid proteins that are transferred along with sperm (the 'transferome') in fruit flies. The products of transferome genes are core determinants of reproductive success and, to date, only transcription factors have been implicated in the modulation of their expression. Hence, as yet, we know nothing about the post-transcriptional mechanisms underlying the tight, responsive and precise regulation of this important gene set. We investigated this omission in the current study. We first used bioinformatics to identify potential regulatory motifs that linked the transferome genes in a putative interaction network. This predicted the presence of putative microRNA (miRNA) 'hubs'. We then tested this prediction, that post-transcriptional regulation is important for the control of transferome genes, by knocking down miRNA expression in adult males. This abolished the ability of males to respond adaptively to the threat of sexual competition, indicating a regulatory role for miRNAs in the regulation of transferome function. Further bioinformatics analysis then identified candidate miRNAs as putative regulatory hubs and evidence for variation in the strength of miRNA regulation across the transferome gene set. The results revealed regulatory mechanisms that can underpin robust, precise and flexible regulation of multiple fitness-related genes. They also help to explain how males can adaptively modulate ejaculate composition.
高度精确的、灵活的和响应的基因表达协调，为许多重要功能的完整性提供了基础。然而，由于缺乏可实验操作的系统、由于涉及的大量基因带来的重大计算挑战，或者由于基因相互作用的准确识别和特征描述存在困难，我们对基因调控网络（GRN）的理解往往受到阻碍。在这里，我们使用了一个可实验操作的实验系统来研究 GRN：即编码与精子一起转移的精液蛋白的基因（“转座体”）在果蝇中的作用。转座体基因的产物是生殖成功的核心决定因素，到目前为止，只有转录因子被认为参与了它们表达的调节。因此，迄今为止，我们对这个重要基因集的紧密、响应和精确调节的转录后机制一无所知。在当前的研究中，我们调查了这一遗漏。我们首先使用生物信息学方法来识别潜在的调控基序，这些基序将转座体基因链接在一个假定的相互作用网络中。这预测了存在潜在的 microRNA (miRNA) “枢纽”。然后，我们通过在成年雄性中敲低 miRNA 的表达来测试这一预测，即转录后调控对于转座体基因的控制很重要。这消除了雄性适应性地对性竞争威胁做出反应的能力，表明 miRNA 在转座体基因功能调控中起调节作用。进一步的生物信息学分析随后确定了候选 miRNA 作为潜在的调节枢纽，并为 miRNA 对转座体基因集的调控强度的变化提供了证据。研究结果揭示了可以为多个与适应性相关的基因的稳健、精确和灵活调节提供基础的调控机制。它们还有助于解释为什么雄性可以自适应地调节精液成分。
