Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Adar1 Knockout Mice DOI Creative Commons
Lisa Zerad, Nadjet Gacem,

Fanny Gayda

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1952 - 1952

Published: Nov. 23, 2024

Adenosine deaminase acting on RNA 1 (ADAR1) is the principal enzyme for adenosine-to-inosine editing that prevents aberrant activation of cytosolic nucleic acid sensors by endogenous double stranded RNAs and interferon-stimulated genes. In mice, conditional neural crest deletion Adar1 reduces survival melanocytes alters differentiation Schwann cells fail to myelinate nerve fibers in peripheral nervous system. These myelination defects are partially rescued upon concomitant removal Mda5 antiviral dsRNA sensor vitro, suggesting implication Mda5/Mavs pathway downstream effectors genesis mutant phenotypes. By analyzing RNA-Seq data from sciatic nerves mouse pups after (Adar1cKO), we here identified transcription factors deregulated Adar1cKO mutants compared controls. Through Adar1;Mavs Adar1cKO;Egr1 double-mutant rescue analyses, then highlighted Mavs adapter protein overexpression early growth response (EGR1) factor contribute associated cell development vivo. silico vitro gene regulation studies additionally suggested EGR1 might mediate this inhibitory effect through EGR2-regulated myelin We thus demonstrate role pathway, but also Adar1-associated defects.

Language: Английский

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

Citations

1
Bacteriophage derived dsRNA induces polarized activation of alveolar macrophages from Balb/c and C57Bl/6 mice in vitro in sex- and age-dependent manner DOI
R. Dovhyi,

A. Dvukhriadkina,

K. Ostrovska

et al.

Cellular Immunology, Journal Year: 2025, Volume and Issue: 408, P. 104916 - 104916

Published: Jan. 4, 2025

Language: Английский

Citations

1
ADAR1 p150 prevents HSV-1 from triggering PKR/eIF2α-mediated translational arrest and is required for efficient viral replication DOI Creative Commons

Adwait Parchure,

Mia Cesarec,

Antonija Braut

et al.

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(4), P. e1012452 - e1012452

Published: April 8, 2025

Adenosine deaminase acting on dsRNA 1 (ADAR1) catalyzes the deamination of adenosines to inosines in double-stranded RNAs (dsRNA) and regulates innate immunity by preventing hyperactivation cytosolic sensors such as MDA5, PKR or ZBP1. ADAR1 has been shown exert pro- antiviral, editing-dependent editing-independent functions viral infections, but little is known about its function herpesvirus replication. We now demonstrate that herpes simplex virus (HSV-1) hyperactivates absence ADAR1, resulting eIF2α mediated translational arrest reduced Silencing inhibition downstream effectors (ICP34.5) pharmacological (ISRIB) inhibitors rescues replication ADAR1-deficient cells. Upon infection, p150 interacts with prevents hyperactivation. Our findings an important proviral factor raises activation threshold for immunity.

Language: Английский

Citations

0
Adenosine-to-inosine RNA editing in cancer: molecular mechanisms and downstream targets DOI Creative Commons
Hao Cheng, Jun Yu, Chi Chun Wong

et al.

Protein & Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 8, 2024

Abstract Adenosine-to-inosine (A-to-I), one of the most prevalent RNA modifications, has recently garnered significant attention. The A-to-I modification actively contributes to biological and pathological processes by affecting structure function various molecules, including double-stranded RNA, transfer microRNA, viral RNA. Increasing evidence suggests that plays a crucial role in development human disease, particularly cancer, aberrant levels are closely associated with tumorigenesis progression through regulation expression multiple oncogenes tumor suppressor genes. Currently, underlying molecular mechanisms cancer not comprehensively understood. Here, we review latest advances regarding editing pathways implicated describing their functions connections disease.

Language: Английский

Citations

1
ADAR1 p150 prevents HSV-1 from triggering PKR/eIF2α-mediated translational arrest and is required for efficient viral replication DOI Creative Commons

Adwait Parchure,

Mia Cesarec,

Vlatka Ivanišević

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 29, 2024

Abstract Adenosine deaminase acting on dsRNA 1 (ADAR1) catalyzes the deamination of adenosines to inosines in double-stranded RNAs (dsRNA) and regulates innate immunity by preventing hyperactivation cytosolic sensors such as MDA5, PKR or ZBP1. ADAR1 has been shown exert pro- antiviral, editing-dependent editing-independent functions viral infections, but little is known about its function herpesvirus replication. We now demonstrate that herpes simplex virus (HSV-1) hyperactivates absence ADAR1, resulting eIF2α mediated translational arrest reduced Silencing inhibition downstream signaling pathways (ICP34.5) pharmacological (ISRIB) inhibitors rescues replication ADAR1-deficient cells. Upon infection, p150 directly interacts with prevents overactivation. Our findings an important proviral factor raises activation threshold for immunity.

Language: Английский

Citations

0
Mapping multiple RNA modifications simultaneously by proximity barcode sequencing DOI Creative Commons
Erdem Sendinc, Hua Yu, Yu Fu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

RNA is subject to a multitude of different chemical modifications that collectively represent the epitranscriptome. Individual including N6-methyladenosine (m

Language: Английский

Citations

0
Past, Present, and Future of RNA Modifications in Infectious Disease Research DOI
Xiaoqing Pan, Alexander Bruch, Matthew G. Blango

et al.

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

In early 2024, the National Academies of Sciences, Engineering, and Medicine (NASEM) released a roadmap for future research into mapping ribonucleic acid (RNA) modifications, which underscored importance better defining these diverse chemical changes to RNA macromolecule. As nearly all mature molecules harbor some form modification, we must understand modifications fully appreciate functionality RNA. The NASEM report calls massive mobilization resources investment akin transformative Human Genome Project 1990s. Like Project, concerted effort in improving our ability assess every single modification on molecule an organism will change way approach biological questions, accelerate technological advance, improve understanding molecular world. Consequently, are also at start revolution impact context host–microbe even microbe–microbe interactions. this perspective, briefly introduce infection biologist, highlight key aspects exciting examples contributing host pathogen biology, finally postulate where infectious disease may benefit from new endeavor globally modifications.

Language: Английский

Citations

0
Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Adar1 Knockout Mice DOI Creative Commons
Lisa Zerad, Nadjet Gacem,

Fanny Gayda

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1952 - 1952

Published: Nov. 23, 2024

Adenosine deaminase acting on RNA 1 (ADAR1) is the principal enzyme for adenosine-to-inosine editing that prevents aberrant activation of cytosolic nucleic acid sensors by endogenous double stranded RNAs and interferon-stimulated genes. In mice, conditional neural crest deletion Adar1 reduces survival melanocytes alters differentiation Schwann cells fail to myelinate nerve fibers in peripheral nervous system. These myelination defects are partially rescued upon concomitant removal Mda5 antiviral dsRNA sensor vitro, suggesting implication Mda5/Mavs pathway downstream effectors genesis mutant phenotypes. By analyzing RNA-Seq data from sciatic nerves mouse pups after (Adar1cKO), we here identified transcription factors deregulated Adar1cKO mutants compared controls. Through Adar1;Mavs Adar1cKO;Egr1 double-mutant rescue analyses, then highlighted Mavs adapter protein overexpression early growth response (EGR1) factor contribute associated cell development vivo. silico vitro gene regulation studies additionally suggested EGR1 might mediate this inhibitory effect through EGR2-regulated myelin We thus demonstrate role pathway, but also Adar1-associated defects.

Language: Английский

Citations

0