Schiksnis Erin C, Nicastro Ian A, Pasquinelli Amy E
Department of Molecular Biology, School of Biological Sciences, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0349, USA.
Nucleic Acids Res. 2024 Dec 11;52(22):13896-13913. doi: 10.1093/nar/gkae1064.
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.
机体衰老的特征是细胞功能和结构衰退，最终导致死亡。为了深入了解这种退化背后的机制，我们在秀丽隐杆线虫的成年期进行了标准RNA测序（RNA-seq）和牛津纳米孔技术直接RNA测序。长读长使得我们能够鉴定出数百种新的异构体以及与年龄相关的异构体差异积累，这是由可变剪接和末端外显子选择导致的。全基因组分析揭示了RNA加工保真度的下降。最后，我们在全基因组范围内鉴定出数千个肌苷和数百个假尿苷编辑。在这张秀丽隐杆线虫假尿苷修饰的首张图谱中，我们发现它们主要位于编码序列中，并且具有这种修饰的基因数量随年龄增长而增加。总的来说，这项分析发现了与年龄相关的转录组特征，是理解众多决定衰老过程中基因表达模式改变和转录后调控的过程的宝贵资源。
