Increased processing of SINE B2 ncRNAs unveils a novel type of transcriptome deregulation in amyloid beta neuropathology.
Increased processing of SINE B2 ncRNAs unveils a novel type of transcriptome deregulation in amyloid beta neuropathology.
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SINE B2 ncRNA的加工增加揭示了淀粉样蛋白β神经病理学中一种新型的转录组失调。
DOI：
10.7554/elife.61265
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发表时间：
2020-11-16
期刊：
影响因子：
7.7
通讯作者：
Zovoilis A
中科院分区：
文献类型：
--
作者：
Cheng Y;Saville L;Gollen B;Isaac C;Belay A;Mehla J;Patel K;Thakor N;Mohajerani MH;Zovoilis A
许多由重复元件产生的非编码rna （ncRNAs）的功能重要性及其与病理过程的联系仍然难以捉摸。B2 rna是sin重复序列B2家族的一类ncRNAs，通过加工各种基因的转录激活来介导应激反应。在这里，我们发现，由于B2 RNA加工水平的增加，这种反应在小鼠海马淀粉样蛋白毒性和病理过程中功能失调，导致B2 RNA靶基因表达的组成性升高和高Trp53水平。有证据表明，应激反应的主要调节因子Hsf1介导海马细胞的B2 RNA加工，并在淀粉样蛋白毒性过程中被激活，加速了SINE RNA的加工和基因的超激活。我们的研究表明，在小鼠中，SINE rna在淀粉样蛋白病理中构成了一种新的通路，对人类大脑中的类似病例，如阿尔茨海默病（AD）有潜在的影响。
The functional importance of many non-coding RNAs (ncRNAs) generated by repetitive elements and their connection with pathologic processes remains elusive. B2 RNAs, a class of ncRNAs of the B2 family of SINE repeats, mediate through their processing the transcriptional activation of various genes in response to stress. Here, we show that this response is dysfunctional during amyloid beta toxicity and pathology in the mouse hippocampus due to increased levels of B2 RNA processing, leading to constitutively elevated B2 RNA target gene expression and high Trp53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in hippocampal cells and is activated during amyloid toxicity, accelerating the processing of SINE RNAs and gene hyper-activation. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimer’s disease (AD).