{"database":"ENA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["Zhongshan Hospital, Fudan University"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA1012848"],"long_description":["Background: Alveolar macrophage (AM) plays an important role in LPS (lipopolysaccharide)-related acute lung injury (ALI). Accumulating evidence suggests that AM-derived exosomes act as a fundamental link between AM-driven inflammation and tissue damage. Our previous work uncovered that AM-derived exosomal tRF-22-8BWS7K092 (tRF-22) could induce ferroptosis in ALI. However, the underlying mechanisms and its exact biological functions in ALI remain obscure.Methods: MLE-12 cells were co-cultured with macrophage-derived exosomes to further confirm the results of in vivo animal study and explore the potential mechanisms involved. The candidate RNA-binding proteins were detected by RNA pull-down and mass spectrometry. The mRNA stability was analyzed using Actinomycin D and qPCR assay. Functional roles of these molecules were investigated using in vitro experiments including CCK-8, western blot assays, detection of malondialdehyde (MDA), Reactive Oxygen Species (ROS) and labile iron levels. Then rescue experiments were performed to explore effects of tRF-22/IGF2BP3/ZFP36 on LPS-treated cells.Results:The tRF-22 in LPS-exo promoted ferroptosis in MLE-12 cells after in vitro co-culture. IGF2BP3, an m6A (N6-Methyladenosine) reader, was identified to be the RNA binding protein of tRF-22. In addition, RNA sequencing was performed to identify the downstream target genes. Further PCR validation, MeRIP-PCR, and eCLIP-seq analysis based on the ENCODE database identified ZFP36 as an important target of IGF2BP3. Mechanistic studies demonstrated that IGF2BP3 promoted the stability of ZFP36 mRNA by reading its m6A modification, and tRF-22 regulated ZFP36 mRNA degradation through IGF2BP3. ZFP36 knock-down significantly promoted ferroptosis in MLE-12 cells through evaluation of the ROS, Fe2+, MDA, FTH1, and GPX4 levels. More importantly, functional rescue experiment verified that tRF-22 regulated ferroptosis of alveolar epithelial cells by targeting ZFP36.Conclusions: These findings support a role for AM-derived exosomal tRF-22 induced m6A modification of IGF2BP3 and the subsequent induction of ferroptosis in the pathogenesis of ALI. Our study proposed a complex tRF-22 - IGF2BP3 - ZFP36 regulatory model based on m6A modification and provided insights into the epi-transcriptomic regulation in ALI."],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"","description":"The tRF-22-8BWS7K092 released by macrophage-derived exosomes regulates lipopolysaccharide induced acute lung injury by targeting IGF2BP3/ZFP36 to induce ferroptosis","dates":{"last_updated":"2024-07-24","first_public":"2024-05-11"},"accession":"PRJNA1012848","cross_references":{}}