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ADAR1 suppression causes interferon signaling and transposable element transcript accumulation in human astrocytes. | LitMetric

ADAR1 suppression causes interferon signaling and transposable element transcript accumulation in human astrocytes.

Front Mol Neurosci

Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, United States.

Published: October 2023

AI Article Synopsis

  • - Neuroinflammation is a key factor in brain aging and Alzheimer's disease, but the mechanisms behind it are still not fully understood.
  • - The enzyme ADAR1 may play a significant role in regulating neuroinflammation by controlling the levels of double-stranded RNA (dsRNA), which can trigger inflammatory responses in astrocytes.
  • - Research using RNA sequencing shows that knocking down ADAR1 in human astrocytes leads to increased pro-inflammatory signals and accumulation of transposable element transcripts, indicating that ADAR1 helps prevent harmful inflammation in the context of aging and Alzheimer's.

Article Abstract

Neuroinflammation is a central mechanism of brain aging and Alzheimer's disease (AD), but the exact causes of age- and AD-related neuroinflammation are incompletely understood. One potential modulator of neuroinflammation is the enzyme adenosine deaminase acting on RNA 1 (ADAR1), which regulates the accumulation of endogenous double-stranded RNA (dsRNA), a pro-inflammatory/innate immune activator. However, the role of ADAR1 and its transcriptomic targets in astrocytes, key mediators of neuroinflammation, have not been comprehensively investigated. Here, we knock down ADAR1 in primary human astrocytes via siRNA transfection and use transcriptomics (RNA-seq) to show that this results in: (1) increased expression of type I interferon and pro-inflammatory signaling pathways and (2) an accumulation of transposable element (TE) transcripts with the potential to form dsRNA. We also show that our findings may be clinically relevant, as gene expression declines with brain aging and AD in humans, and this is associated with a similar increase in TE transcripts. Together, our results suggest an important role for ADAR1 in preventing pro-inflammatory activation of astrocytes in response to endogenous dsRNA with aging and AD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685929PMC
http://dx.doi.org/10.3389/fnmol.2023.1263369DOI Listing

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