Kirio Ken, Patop Ines Lucia, Anduaga Ane Martin, Harris Jenna, Pamudurti Nagarjuna, Su The Nandar, Martel Claire, Kadener Sebastian
Biology Department, Brandeis University, Waltham, MA 02454, USA.
Biology Department, Brandeis University, Waltham, MA 02454, USA.
Cell Rep. 2025 Apr 22;44(4):115485. doi: 10.1016/j.celrep.2025.115485. Epub 2025 Apr 2.
Circular RNAs (circRNAs) increase in the brain with age across various animal systems. To elucidate the reasons behind this phenomenon, we profile circRNAs from fly heads at six time points throughout their lifespan. Our results reveal a linear increase in circRNA levels with age, independent of changes in mRNA levels, overall transcription, intron retention, or host gene splicing, demonstrating that the age-related accumulation is due to high stability rather than increased biogenesis. This remarkable stability suggests that circRNAs can serve as markers of environmental experience. Indeed, flies exposed to a 10-day regimen at 29°C exhibit higher levels of specific circRNAs even 6 weeks after returning to standard conditions, indicating that circRNAs can reveal past environmental stimuli. Moreover, half-life measurements show circRNA stability exceeding 20 days, with some displaying virtually no degradation. These findings underscore the remarkable stability of circRNAs in vivo and their potential as markers for stress and life experiences.
在各种动物系统中，环状RNA（circRNAs）在大脑中会随着年龄的增长而增加。为了阐明这一现象背后的原因，我们在果蝇整个生命周期的六个时间点对其头部的circRNAs进行了分析。我们的结果显示，circRNA水平随年龄呈线性增加，与mRNA水平、整体转录、内含子保留或宿主基因剪接的变化无关，这表明与年龄相关的积累是由于高稳定性而非生物合成增加所致。这种显著的稳定性表明circRNAs可以作为环境经历的标志物。事实上，在29°C下接受10天实验方案处理的果蝇，即使在回到标准条件6周后，特定circRNAs的水平仍较高，这表明circRNAs可以揭示过去的环境刺激。此外，半衰期测量显示circRNA的稳定性超过20天，有些几乎没有降解。这些发现强调了circRNAs在体内的显著稳定性及其作为应激和生活经历标志物的潜力。
