Truby Natalie L, Smith Corinne, Hamilton Peter J
Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
bioRxiv. 2025 Jan 24:2025.01.22.634143. doi: 10.1101/2025.01.22.634143.
Transposable elements (TEs) are repetitive DNA sequences capable of being transcribed and reintegrated, or transposed, into distinct loci throughout the genome. While thought to be largely transcriptionally silenced in brain, TE transcription is increasingly recognized as dynamic and involved in human health and disease states, including in disorders of the brain. In this study, we annotated TE transcripts in publicly available RNA sequencing (RNAseq) of postmortem human brain tissue to investigate the expression profile of TE transcripts in individuals with Major Depressive Disorder (MDD) compared to healthy controls. Our findings reveal a robust and uniform downregulation of TE transcript expression in the brains of subjects with MDD relative to controls, this occurs most prominently in the orbitofrontal cortex (OFC) brain region, and MDD differentially impacts this TE expression by age and sex. This work points to the aberrant transcription of cortical TEs as a potentially overlooked molecular signature of MDD.
转座元件（TEs）是能够转录并重新整合或转座到全基因组不同位点的重复DNA序列。虽然通常认为TEs在大脑中大多处于转录沉默状态，但TE转录越来越被认为是动态的，并参与人类健康和疾病状态，包括脑部疾病。在本研究中，我们对死后人类脑组织的公开可用RNA测序（RNAseq）中的TE转录本进行注释，以研究与健康对照相比，重度抑郁症（MDD）患者中TE转录本的表达谱。我们的研究结果显示，与对照组相比，MDD患者大脑中TE转录本表达出现显著且一致的下调，这在眶额皮质（OFC）脑区最为明显，并且MDD对TE表达的影响因年龄和性别而异。这项工作表明，皮质TEs的异常转录是MDD一个可能被忽视的分子特征。
