mRNA expression dynamics promote and maintain the identity of somatic tissues in living organisms; however, their impact in post-transcriptional gene regulation in these processes is not fully understood. Here, we applied the PAT-Seq approach to systematically isolate, sequence, and map tissue-specific mRNA from five highly studied Caenorhabditis elegans somatic tissues: GABAergic and NMDA neurons, arcade and intestinal valve cells, seam cells, and hypodermal tissues, and studied their mRNA expression dynamics. The integration of these datasets with previously profiled transcriptomes of intestine, pharynx, and body muscle tissues, precisely assigns tissue-specific expression dynamics for 60% of all annotated C. elegans protein-coding genes, providing an important resource for the scientific community. The mapping of 15,956 unique high-quality tissue-specific polyA sites in all eight somatic tissues reveals extensive tissue-specific 3'untranslated region (3'UTR) isoform switching through alternative polyadenylation (APA) . Almost all ubiquitously transcribed genes use APA and harbor miRNA targets in their 3'UTRs, which are commonly lost in a tissue-specific manner, suggesting widespread usage of post-transcriptional gene regulation modulated through APA to fine tune tissue-specific protein expression. Within this pool, the human disease gene C. elegans orthologs rack-1 and tct-1 use APA to switch to shorter 3'UTR isoforms in order to evade miRNA regulation in the body muscle tissue, resulting in increased protein expression needed for proper body muscle function. Our results highlight a major positive regulatory role for APA, allowing genes to counteract miRNA regulation on a tissue-specific basis.

译文

mRNA表达动力学促进并维持活生物体中体细胞组织的身份; 但是,它们在这些过程中对转录后基因调控的影响尚未完全了解。在这里,我们应用PAT-Seq方法从五个高度研究的秀丽隐杆线虫体细胞组织中系统地分离、测序和定位组织特异性mRNA: gaba能和NMDA神经元、拱廊和肠瓣细胞、接缝细胞和皮下组织,并研究了它们的mRNA表达动力学。将这些数据集与先前描述的肠,咽和身体肌肉组织的转录组进行整合,精确地为所有注释的秀丽隐杆线虫蛋白质编码基因的60% 分配了组织特异性表达动力学,为科学界提供了重要的资源。在所有八个体细胞组织中15,956独特的高质量组织特异性polyA位点的作图揭示了通过替代多腺苷酸化 (APA) 进行广泛的组织特异性3' 非翻译区 (3'UTR) 同工型转换。几乎所有普遍转录的基因都使用APA,并在其3'utr中携带miRNA靶标,这些靶标通常以组织特异性方式丢失,这表明广泛使用通过APA调节的转录后基因调控来微调组织特异性蛋白表达。在该池中,人类疾病基因C. elegans直系同源物rack-1和tct-1使用APA切换到较短的3'UTR同工型,以逃避身体肌肉组织中的miRNA调节,导致适当的身体肌肉功能所需的蛋白质表达增加。我们的结果强调了APA的主要积极调节作用,允许基因在组织特异性的基础上抵消miRNA的调节。

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