Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, China; International Center for Aging and Cancer (ICAC), The First Affiliated Hospital, Hainan Medical University, Haikou, China.
Trends Biochem Sci. 2023 Jul;48(7):618-628. doi: 10.1016/j.tibs.2023.03.007. Epub 2023 Apr 15.
During cellular senescence and organismal aging, cells display various molecular and morphological changes. Although many aging-related long noncoding RNAs (lncRNAs) are highly associated with senescence-associated secretory phenotype, the roles of lncRNAs in senescence-associated nuclear architecture and morphological changes are just starting to emerge. Here I review lncRNAs associated with nuclear structure establishment and maintenance, their aging-related changes, and then focus on the pervasive, yet underappreciated, role of RNA double-strand DNA triplexes for lncRNAs to recognize targeted genomic regions, making lncRNAs the nexus between DNA and proteins to regulate nuclear structural changes. Finally, I discuss the future of deciphering direct links of lncRNA changes to various nuclear morphology changes assisted by artificial intelligence and genetic perturbations.
在细胞衰老和生物体老化过程中，细胞会表现出各种分子和形态变化。虽然许多与衰老相关的长链非编码 RNA（lncRNA）与衰老相关的分泌表型高度相关，但 lncRNA 在衰老相关的核结构和形态变化中的作用才刚刚开始显现。在这里，我回顾了与核结构建立和维持相关的 lncRNA，以及它们与衰老相关的变化，然后重点介绍了 RNA 双链-DNA 三链体的普遍存在但尚未被充分认识的作用，以便 lncRNA 识别靶向基因组区域，使 lncRNA 成为连接 DNA 和蛋白质以调节核结构变化的纽带。最后，我讨论了借助人工智能和遗传扰动来阐明 lncRNA 变化与各种核形态变化之间直接联系的未来。
