Increased unedited Alu RNA patterns found in cortex extracellular vesicles in Alzheimer's disease resemble hippocampus vasculature Alu RNA editing patterns but not cortex Alu RNA editing patterns.

Background: Endogenous Alu RNAs form double-stranded RNAs recognized by double-stranded RNA sensors and activate IRF and NF-kB transcriptional paths and innate immunity. Deamination of adenosines to inosines by the ADAR family of enzymes, a process termed A-to-I editing, disrupts double-stranded RNA structure and prevents innate immune activation. Innate immune activation is observed in Alzheimer's disease, the most common form of dementia.

Nanoparticle Delivery of Immunostimulatory Alu RNA for Cancer Immunotherapy.

Unlabelled: It was recently found that patients with relapsing remitting multiple sclerosis exhibit widespread loss of adenosine-to-inosine (A-to-I) RNA editing, which contributes to the accumulation of immunostimulatory double-stranded Alu RNA in circulating leukocytes and an attendant increase in levels of proinflammatory cytokines (e.g., type I IFNs).

Reduced RNA adenosine-to-inosine editing in hippocampus vasculature associated with Alzheimer's disease.

Alzheimer's disease is the most common form of dementia and recent studies identify a type 1 interferon response in Alzheimer's disease possibly driving neuro-inflammation and other Alzheimer's disease pathologies. Loss of adenosine-to-inosine editing of endogenous Alu RNAs results in accumulation of Alu double-stranded RNAs, activation of double-stranded RNA sensors, and induction of interferon and nuclear factor kappa B regulated genes. Here, we investigated if changes in adenosine-to-inosine editing were associated with presence of Alzheimer's disease in total prefrontal cortex, total hippocampus, cortex vasculature and hippocampus vasculature using available RNA sequencing files.

Alu RNA Structural Features Modulate Immune Cell Activation and A-to-I Editing of Alu RNAs Is Diminished in Human Inflammatory Bowel Disease.

Alu retrotransposons belong to the class of short interspersed nuclear elements (SINEs). Alu RNA is abundant in cells and its repetitive structure forms double-stranded RNAs (dsRNA) that activate dsRNA sensors and trigger innate immune responses with significant pathological consequences. Mechanisms to prevent innate immune activation include deamination of adenosines to inosines in dsRNAs, referred to as A-to-I editing, degradation of Alu RNAs by endoribonucleases, and sequestration of Alu RNAs by RNA binding proteins.

Reduced A-to-I editing of endogenous Alu RNAs in lung after SARS-CoV-2 infection.

Due to potential severity of disease caused by SARS-CoV-2 infection, it is critical to understand both mechanisms of viral pathogenesis as well as diversity of host responses to infection. Reduced A-to-I editing of endogenous double-stranded RNAs (dsRNAs), as a result of inactivating mutations in , produces one form of Aicardi-Goutières Syndrome, with an immune response similar to an anti-viral response. By analyzing whole genome RNA sequencing data, we find reduced levels of A-to-I editing of endogenous Alu RNAs in normal human lung cells after infection by SARS-CoV-2 as well as in lung biopsies from patients with SARS-CoV-2 infections.