Dissecting the role of B2 SINE RNA processing in activation of stress response genes in mouse brain amyloid and aging pathology

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Isaac, Christopher
University of Lethbridge. Faculty of Arts and Science
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Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry & Biochemistry
Alzheimer's disease (AD) is a neurodegenerative disorder that results in impairment of learning and memory. Previous work in mice has shown that learning correlates with hippocampus–specific changes in expression of stress response genes (SRGs) and that excess expression of SRGs results in apoptosis. Many mouse SRGs are regulated by a non-coding SINE RNA called B2, but it is unclear how SINE RNAs contribute to AD overall. In this work we show via RNAseq that there is abnormal hyperactivation of SRGs caused by dysregulation of the B2-mediated stress response mouse amyloid-aging pathology. We also show that B2 RNA degradation is abnormally high during active neurodegeneration and that the increase in B2 degradation is due to Hsf1-mediated cleavage of B2 RNA during amyloid beta-induced stress. Our research reveals a novel connection between abnormal SINE RNA processing, SRG hyper-activation, and amyloid-aging pathology. Further study of SINE RNAs may elucidate new AD therapies.
Alzheimer's disease , Amyloid , RNA , Stress (Physiology) -- Animal models , Stress (Physiology) -- Molecular aspects