TY - JOUR
T1 - Increased processing of sine b2 ncrnas unveils a novel type of transcriptome deregulation in amyloid beta neuropathology
AU - Cheng, Yubo
AU - Saville, Luke
AU - Gollen, Babita
AU - Isaac, Christopher
AU - Belay, Abel
AU - Mehla, Jogender
AU - Patel, Kush
AU - Thakor, Nehal
AU - Mohajerani, Majid H.
AU - Zovoilis, Athanasios
N1 - Publisher Copyright:
© Cheng et al.
PY - 2020/10
Y1 - 2020/10
N2 - 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).
AB - 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).
UR - https://www.scopus.com/pages/publications/85097210469
U2 - 10.7554/eLife.61265
DO - 10.7554/eLife.61265
M3 - Article
C2 - 33191914
AN - SCOPUS:85097210469
SN - 2050-084X
VL - 9
SP - 1
EP - 32
JO - eLife
JF - eLife
M1 - e61265
ER -