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Spinal cord ischemia-reperfusion injury (SCIRI) leads to severe neurological deficits, with pyroptosis emerging as a key driver of inflammation and neuronal death. Recent studies suggest that methyltransferase-like 3 (METTL3), a critical RNA methyltransferase, may regulate the nucleotide-binding oligomerized structural domain-like receptor protein 3 (NLRP3) inflammasome activation via N6-Methyladenosine (m6A) modification, yet direct evidence in SCIRI remains limited. This review synthesizes current knowledge on the METTL3-NLRP3 axis in pyroptosis, explores its therapeutic potential, and identifies critical research gaps for future investigation.
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http://dx.doi.org/10.3389/fimmu.2025.1552704 | DOI Listing |
Nat Struct Mol Biol
September 2025
Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, UK.
X-chromosome inactivation (XCI) in mammals is orchestrated by the noncoding RNA X-inactive-specific transcript (Xist) that, together with specific interacting proteins, functions in cis to silence an entire X chromosome. Defined sites on Xist RNA carry the N-methyladenosine (mA) modification and perturbation of the mA writer complex has been found to abrogate Xist-mediated gene silencing. However, the relative contribution of mA and its mechanism of action remain unclear.
View Article and Find Full Text PDFJ Gastroenterol
September 2025
Department of General Surgery (Hepatopancreatobiliary Surgery), Department of Biliary-Pancreatic Center, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou City, 646000, Sichuan Province, China.
Background And Aims: Inflammatory cell infiltration in the liver is a hallmark of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the pathological events that trigger the infiltration of inflammatory cells to mediate MAFLD pathogenesis remains poorly understood. This study aims to investigate the function and mechanism of Hic-5 on hepatic inflammation of MAFLD.
View Article and Find Full Text PDFFASEB J
September 2025
Department of Hematology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
Epilepsy is a common chronic nervous system disease that threatens human health. However, the role of FOXC1 and its relations with pyroptosis have not been fully studied in epilepsy. Sprague-Dawley rats were obtained for constructing temporal lobe epilepsy (TLE) models.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
September 2025
Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Heat shock protein family A member 4-like (HSPA4L) has been shown to be overexpressed in osteoarthritis (OA) patients, but its role in OA process still unknown. Chondrocytes were stimulated with interleukin-1β (IL-1β) to mimic OA cell model in vitro, and rat was injected with monosodium iodoacetate (MIA) to construct OA rat model in vivo. The expression of HSPA4L, methyltransferase-like 3 (METTL3) and extracellular matrix (ECM)-related markers was examined by qRT-PCR or western blot.
View Article and Find Full Text PDFMol Ther
September 2025
Xi'an No. 1 Hospital, First Affiliated Hospital of Northwest University, School of Medicine, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology of Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an,
N6-methyladenosine (mA) modification, primarily regulated by methyltransferase-like protein 3 (METTL3), plays a pivotal role in RNA metabolism and leukemogenesis. However, the post-translational mechanisms governing METTL3 stability and function remain incompletely understood. Given the widespread occurrence of O-GlcNAcylation on nuclear and cytosolic proteins, we hypothesized that METTL3 might undergo O-GlcNAcylation, thereby influencing its stability and oncogenic function in myeloid malignancies.
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