A Wonderful Journey: The Diverse Roles of Adenosine Deaminase Action on RNA 1 (ADAR1) in Central Nervous System Diseases DOI Creative Commons
Lin Cheng, Ziying Liu,

Chunxiao Shen

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 1, 2025

ABSTRACT Background Adenosine deaminase action on RNA 1 (ADAR1) can convert the adenosine in double‐stranded (dsRNA) molecules into inosine a process known as A‐to‐I editing. ADAR1 regulates gene expression output by interacting with and other proteins; plays important roles development, including growth; is linked to innate immunity, tumors, central nervous system (CNS) diseases. Results In recent years, role of tumors has been widely discussed, but its CNS diseases not reviewed. It worth noting that studies have shown great potential treatment neurodegenerative diseases, mechanisms are still unclear. Therefore, it necessary elaborate Conclusions Here, we focus effects such Aicardi–AicardiGoutières syndrome, Alzheimer's disease, Parkinson's glioblastoma, epilepsy, amyotrophic lateral sclerosis, autism. We also evaluate impact ADAR1‐based strategies these particular development new technologies microRNAs, nanotechnology, editing, stem cell therapy. hope provide directions insights for future editing technology brain science

Language: Английский

Writers, readers, and erasers RNA modifications and drug resistance in cancer DOI Creative Commons
Di Chen, Xinyu Gu,

Yeltai Nurzat

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

Citations

18
Z‐Nucleic Acid Sensing and Activation of ZBP1 in Cellular Physiology and Disease Pathogenesis DOI Open Access

Sanchita Mishra,

Ayushi Amin Dey,

Sannula Kesavardhana

et al.

Immunological Reviews, Journal Year: 2025, Volume and Issue: 329(1)

Published: Jan. 1, 2025

ABSTRACT Z‐nucleic acid binding protein 1 (ZBP1) is an innate immune sensor recognizing nucleic acids in Z‐conformation. Upon sensing, ZBP1 triggers activation, inflammation, and programmed cell death during viral infections, mice development, inflammation‐associated diseases. The Zα domains of sense promote RIP‐homotypic interaction motif (RHIM)‐dependent signaling complex assembly to mount inflammation. studies on spurred understanding the role Z‐form RNA DNA cellular physiological functions. In particular, short genomic segments, endogenous retroviral elements, 3′UTR regions are likely sources Z‐RNAs that orchestrate Recent seminal identify intriguing association with adenosine deaminase acting RNA‐1 (ADAR1), cyclic GMP‐AMP synthase (cGAS) regulating aberrant chronic cancer. Thus, attractive target aid development specific therapeutic regimes for disease biology. Here, we discuss Z‐RNA activation death, Also, how coordinates intracellular perturbations homeostasis, formation regulate diseases

Language: Английский

Citations

2
Viral Z-RNA triggers ZBP1-dependent cell death DOI
Siddharth Balachandran, Edward S. Mocarski

Current Opinion in Virology, Journal Year: 2021, Volume and Issue: 51, P. 134 - 140

Published: Oct. 22, 2021

Language: Английский

Citations

63
RNA editing at a limited number of sites is sufficient to prevent MDA5 activation in the mouse brain DOI Creative Commons

Jung In Kim,

Taisuke Nakahama,

Ryuichiro Yamasaki

et al.

PLoS Genetics, Journal Year: 2021, Volume and Issue: 17(5), P. e1009516 - e1009516

Published: May 13, 2021

Adenosine deaminase acting on RNA 1 (ADAR1), an enzyme responsible for adenosine-to-inosine editing, is composed of two isoforms: nuclear p110 and cytoplasmic p150. Deletion Adar1 or p150 genes in mice results embryonic lethality with overexpression interferon-stimulating (ISGs), caused by the aberrant recognition unedited endogenous transcripts melanoma differentiation-associated protein 5 (MDA5). However, among numerous editing sites, how many sites require especially ADAR1 p150, to avoid MDA5 activation whether contributes this function remains elusive. In particular, abundant mouse brain where a subtle amount expressed, whereas mutations cause Aicardi–Goutières syndrome, which one most affected organs accompanied elevated expression ISGs. Therefore, understanding editing–mediated prevention important. Here, we established –specific knockout mice, upregulated ISGs was not observed. This result suggests that p150–mediated enough suppress activation. further created / Adar2 double identify sites. analysis demonstrated although observed, only less than 2% were preserved brains mice. Of note, found some highly edited, comparable those wild-type indicating presence p150–specific These data suggest at very limited mediated sufficient prevents activation, least brain.

Language: Английский

Citations

59
RNA sensing via the RIG‐I‐like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency DOI Creative Commons
Jorn E. Stok, Timo Oosenbrug, Laurens R. ter Haar

et al.

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(6)

Published: Feb. 14, 2022

Language: Английский

Citations

43
The Z-nucleic acid sensor ZBP1 in health and disease DOI Creative Commons
Jonathan Maelfait, Jan Rehwinkel

The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 220(8)

Published: July 14, 2023

Nucleic acid sensing is a central process in the immune system, with far-reaching roles antiviral defense, autoinflammation, and cancer. Z-DNA binding protein 1 (ZBP1) sensor for double-stranded DNA RNA helices unusual left-handed Z conformation termed Z-RNA. Recent research established ZBP1 as key upstream regulator of cell death proinflammatory signaling. Recognition Z-DNA/RNA by promotes host resistance to viral infection but can also drive detrimental autoinflammation. Additionally, has interesting cancer other disease settings emerging an attractive target therapy.

Language: Английский

Citations

39
Detection of alternative DNA structures and its implications for human disease DOI Creative Commons
Gabriel Matos‐Rodrigues, Julia A. Hisey,

André Nussenzweig

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(20), P. 3622 - 3641

Published: Oct. 1, 2023

Language: Английский

Citations

37
Long 3′UTRs predispose neurons to inflammation by promoting immunostimulatory double-stranded RNA formation DOI
Tyler J. Dorrity, Heegwon Shin, K Wiegand

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(88)

Published: Oct. 20, 2023

Loss of RNA homeostasis underlies numerous neurodegenerative and neuroinflammatory diseases. However, the molecular mechanisms that trigger neuroinflammation are poorly understood. Viral double-stranded (dsRNA) triggers innate immune responses when sensed by host pattern recognition receptors (PRRs) present in all cell types. Here, we report human neurons intrinsically carry exceptionally high levels immunostimulatory dsRNAs identify long 3'UTRs as giving rise to neuronal dsRNA structures. We found neuron-enriched ELAVL family genes (

Language: Английский

Citations

36
The ADAR1 editome reveals drivers of editing-specificity for ADAR1-isoforms DOI Creative Commons

Renata Kleinová,

Vinod Rajendra,

Alina F. Leuchtenberger

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(9), P. 4191 - 4207

Published: April 7, 2023

Adenosine deaminase acting on RNA ADAR1 promotes A-to-I conversion in double-stranded and structured RNAs. has two isoforms transcribed from different promoters: cytoplasmic ADAR1p150 is interferon-inducible while ADAR1p110 constitutively expressed primarily localized the nucleus. Mutations cause Aicardi - Goutières syndrome (AGS), a severe autoinflammatory disease associated with aberrant IFN production. In mice, deletion of or p150 isoform leads to embryonic lethality driven by overexpression interferon-stimulated genes. This phenotype rescued dsRNA-sensor MDA5 indicating that indispensable cannot be ADAR1p110. Nevertheless, editing sites uniquely targeted remain elusive. Here, transfection into ADAR-less mouse cells we detect isoform-specific patterns. Using mutated ADAR variants, test how intracellular localization presence Z-DNA binding domain-α affect preferences. These data show ZBDα only minimally contributes editing-specificity directed isoforms. Our study complemented RIP-seq human ectopically expressing tagged-ADAR1 Both datasets reveal enrichment intronic preferentially binds edits 3'UTRs.

Language: Английский

Citations

30
Novel insights into double-stranded RNA-mediated immunopathology DOI
Richard de Reuver, Jonathan Maelfait

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 24(4), P. 235 - 249

Published: Sept. 26, 2023

Language: Английский

Citations

30