Hu Muhan, Crossman David, Prasain Jeevan K, Miller Michael A, Serra Rosa A
Department of Cell Development and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Genes (Basel). 2020 Mar 9;11(3):288. doi: 10.3390/genes11030288.
The transforming growth factor beta superfamily encompasses a large family of ligands that are well conserved across many organisms. They are regulators of a number of physiological and pathological processes. The model nematode has been instrumental in identifying key components of the transforming growth factor beta (TGFβ) pathway. In , the TGFβ homolog DAF-7 signals through the DAF-1 Type I and DAF-4 Type II receptors to phosphorylate downstream R-SMADs DAF-8 and DAF-14. These R-SMADs translocate into the nucleus to inhibit Co-SMAD DAF-3. Many of the roles of the canonical DAF-7 pathway, involving both DAF-1 and DAF-3, have been identified using targeted genetic studies. Few have assessed the global transcriptomic changes in response to these genes, especially in adult animals. In this study, we performed RNA sequencing on wild type, , and ; adult hermaphrodites. To assess the overall trends of the data, we identified differentially expressed genes (DEGs) and performed gene ontology analysis to identify the types of downstream genes that are differentially expressed. Hierarchical clustering showed that the ; double mutants are transcriptionally more similar to wild type than mutants. Analysis of the DEGs showed a disproportionally high number of genes whose expression is increased in mutants, suggesting that DAF-1 acts as a general repressor of gene expression in wild type animals. Gene ontology analysis of the DEGs produced many significantly enriched terms, including Molting Cycle, Response to Topologically Incorrect Protein, and Response to Biotic Stimulus. Understanding the direct and indirect targets of the DAF-7 TGFβ pathway through this RNA-seq dataset can provide insight into novel roles of the multifunctional signaling pathway, as well as identify novel genes that may participate in previously reported functions of TGFβ signaling.
转化生长因子β超家族包含一大类在许多生物体中高度保守的配体。它们是多种生理和病理过程的调节因子。模式线虫在鉴定转化生长因子β（TGFβ）信号通路的关键组成部分方面发挥了重要作用。在该线虫中，TGFβ同源物DAF - 7通过DAF - 1 I型受体和DAF - 4 II型受体发出信号，使下游的R - SMADs DAF - 8和DAF - 14磷酸化。这些R - SMADs易位进入细胞核以抑制共SMAD DAF - 3。使用靶向基因研究已经确定了经典DAF - 7信号通路中涉及DAF - 1和DAF - 3的许多作用。很少有研究评估响应这些基因的全局转录组变化，特别是在成年动物中。在本研究中，我们对野生型、[此处原文缺失相关突变体信息]和[此处原文缺失相关突变体信息]成年雌雄同体线虫进行了RNA测序。为了评估数据的总体趋势，我们鉴定了差异表达基因（DEGs）并进行了基因本体分析，以确定差异表达的下游基因类型。层次聚类显示，[此处原文缺失相关突变体信息]双突变体在转录水平上比[此处原文缺失相关突变体信息]突变体更类似于野生型。对DEGs的分析表明，在[此处原文缺失相关突变体信息]突变体中表达增加的基因数量异常多，这表明DAF - 1在野生型动物中作为基因表达的一般抑制因子发挥作用。对DEGs的基因本体分析产生了许多显著富集的术语，包括蜕皮周期、对拓扑结构错误蛋白质的反应和对生物刺激的反应。通过这个RNA - seq数据集了解DAF - 7 TGFβ信号通路的直接和间接靶点，可以深入了解多功能信号通路的新作用，并识别可能参与TGFβ信号先前报道功能的新基因。
