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 (RNA-seq) and Oxford Nanopore Technologies direct RNA-seq 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. Finally, we identify thousands of inosine and hundreds of pseudouridine edits genome-wide. 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.

中文翻译：

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全长直接 RNA 测序揭示了衰老秀丽隐杆线虫中 RNA 表达、加工和修饰的广泛重塑


机体衰老的特点是细胞功能和解剖结构下降，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的成年时间过程中进行了标准 RNA 测序 （RNA-seq） 和 Oxford Nanopore Technologies 直接 RNA-seq。长读长可识别数百种新型亚型和年龄相关的差异亚型积累，这是由选择性剪接和末端外显子选择产生的。全基因组分析显示 RNA 加工保真度下降。最后，我们在全基因组范围内鉴定了数千个肌苷和数百个假尿苷编辑。在秀丽隐杆线虫假尿苷修饰的第一张图中，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，该分析发现了与年龄相关的转录组特征，是了解决定衰老中基因表达模式改变和转录后调控的许多过程的宝贵资源。