{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330506/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"," Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330506"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"ac4C stabilizes a G-quadruplex to enforce HBV pgRNA clearance","description":"Hepatitis B virus (HBV) pregenomic RNA (pgRNA) is essential for viral replication, but the host factors that degrade it remain poorly understood. Using ac4C-RIP-seq, CLIP-seq, and RedaC:T-amplicon sequencing, we identify an N4-acetylcytidine (ac4C) RNA modification-dependent pathway that targets HBV pgRNA for decay. We find that ac4C modifications, deposited by NAT10, stabilize a G-quadruplex (G4) structure within pgRNA. This ac4C-stabilized G4 structure is recognized and bound by two RNA-binding proteins, hnRNPH1 and GRSF1. hnRNPH1 binding destabilizes the G4 and accelerates pgRNA decay, while GRSF1 directs the RNA to mitochondria for clearance by the RNA degradosome (PNPase/hSUV3). The viral HBx protein upregulates NAT10, forming a negative feedback loop that restricts HBV replication. Together, our findings reveal a multilayered host surveillance mechanism that eliminates viral pgRNA via RNA modification and structural elements. The ac4C-G4-GRSF1 axis represents a potential therapeutic target for HBV cure.","dates":{"publication":"2026/05/13"},"accession":"GSE330506","cross_references":{"GSM":["GSM9727870","GSM9727850","GSM9727872","GSM9727871","GSM9727852","GSM9727874","GSM9727873","GSM9727851","GSM9727876","GSM9727854","GSM9727853","GSM9727875","GSM9727878","GSM9727856","GSM9727855","GSM9727877","GSM9727858","GSM9727879","GSM9727857","GSM9727838","GSM9727859","GSM9727837","GSM9727839","GSM9727880","GSM9727861","GSM9727860","GSM9727841","GSM9727863","GSM9727862","GSM9727840","GSM9727865","GSM9727843","GSM9727864","GSM9727842","GSM9727867","GSM9727845","GSM9727844","GSM9727866","GSM9727847","GSM9727869","GSM9727868","GSM9727846","GSM9727849","GSM9727848"],"GPL":["20301","15520","16417","29480"],"GSE":["330506"],"taxon":["Mus musculus"," Homo sapiens"]}}