PDF(Pubmed)
Abstract：
Organismal aging is marked by decline in cellular function and anatomy, ultimately resulting in death. To inform our understanding of the mechanisms underlying this degeneration, we performed standard RNA sequencing and Nanopore direct RNA sequencing over an adult time course in Caenorhabditis elegans. Long reads allowed for identification of hundreds of novel isoforms and age-associated differential isoform accumulation, resulting from alternative splicing and terminal exon choice. Genome-wide analysis reveals a decline in RNA processing fidelity and a rise in inosine and pseudouridine editing events in transcripts from older animals. In this first map of pseudouridine modifications for C. elegans, we find that they largely reside in coding sequences and that the number of genes with this modification increases with age. Collectively, this analysis discovers transcriptomic signatures associated with age and is a valuable resource to understand the many processes that dictate altered gene expression patterns and post-transcriptional regulation in aging.
摘要：
器官衰老的标志是细胞功能和解剖学的下降，最终导致死亡。为了让我们了解这种退化的潜在机制，我们在秀丽隐杆线虫中进行了标准RNA测序和纳米孔直接RNA测序。长读数允许鉴定数百种新的同工型和与年龄相关的差异同工型积累，由于选择性剪接和末端外显子选择。全基因组分析显示，RNA加工保真度下降，老年动物转录本的肌苷和假尿苷编辑事件增加。在秀丽隐杆线虫伪尿苷修饰的第一张图谱中，我们发现它们主要存在于编码序列中，并且具有这种修饰的基因数量随着年龄的增长而增加。总的来说，这项分析发现了与年龄相关的转录组特征,是理解衰老过程中基因表达模式和转录后调控改变的许多过程的宝贵资源.
