Nersisyan Stepan, Loher Phillipe, Nazeraj Iliza, Shao Zhiping, Fullard John F, Voloudakis Georgios, Girdhar Kiran, Roussos Panos, Rigoutsos Isidore
Computational Medicine Center, Thomas Jefferson University, Philadelphia, PA, USA.
Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, USA.
bioRxiv. 2024 Dec 25:2024.12.24.630254. doi: 10.1101/2024.12.24.630254.
We investigated small non-coding RNAs (sncRNAs) from the prefrontal cortex of 93 individuals diagnosed with schizophrenia (SCZ) or bipolar disorder (BD) and 77 controls. We uncovered recurring complex sncRNA profiles, with 98% of all sncRNAs being accounted for by miRNA isoforms (60.6%), tRNA-derived fragments (17.8%), rRNA-derived fragments (11.4%), and Y RNA-derived fragments (8.3%). In SCZ, 15% of all sncRNAs exhibit statistically significant changes in their abundance. In BD, the fold changes (FCs) are highly correlated with those in SCZ but less acute. Non-templated nucleotide additions to the 3´-ends of many miRNA isoforms determine their FC independently of miRNA identity or genomic locus of origin. In both SCZ and BD, disease- and age-associated sncRNAs and mRNAs reveal accelerated aging. Co-expression modules between sncRNAs and mRNAs align with the polarities of SCZ changes and implicate sncRNAs in critical processes, including synaptic signaling, neurogenesis, memory, behavior, and cognition.
我们研究了93名被诊断为精神分裂症（SCZ）或双相情感障碍（BD）的个体以及77名对照者前额叶皮质中的小非编码RNA（sncRNA）。我们发现了反复出现的复杂sncRNA谱，所有sncRNA中有98%由miRNA异构体（60.6%）、tRNA衍生片段（17.8%）、rRNA衍生片段（11.4%）和Y RNA衍生片段（8.3%）组成。在SCZ中，所有sncRNA中有15%的丰度表现出统计学上的显著变化。在BD中，倍数变化（FC）与SCZ中的高度相关，但程度较轻。许多miRNA异构体3´端的非模板化核苷酸添加独立于miRNA身份或起源基因组位点决定其FC。在SCZ和BD中，与疾病和年龄相关的sncRNA和mRNA都显示出加速衰老。sncRNA和mRNA之间的共表达模块与SCZ变化的极性一致，并表明sncRNA参与关键过程，包括突触信号传导、神经发生、记忆、行为和认知。
