{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326441/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326441"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"SMD2 reads pseudouridines to regulate mRNA splicing and promote tumorigenesis [RNA-seq]","description":"Pseudouridines (Ψ) in mRNA are linked to alternative splicing, but their regulatory mechanisms remain unclear due to the lack of identified reader proteins. Here, we identify SMD2, a core spliceosomal component, as a direct Ψ reader. Using in vitro and ex vivo assays, we show that SMD2 preferentially binds Ψ over unmodified uridines. SMD2 collaborates with PUS family enzymes to regulate alternative splicing by binding Ψ near exon-intron boundaries, modulating the splicing of numerous pre-mRNAs. Notably, the gene encoding SMD2, SNRPD2, is overexpressed across multiple cancers and is essential for tumor cell proliferation through the maturation of key transcripts. These findings uncover a direct mechanistic link between Ψ and spliceosomal function, establishing SMD2 as a critical regulator of Ψ-mediated splicing and a potential cancer therapeutic target.","dates":{"publication":"2026/06/17"},"accession":"GSE326441","cross_references":{"GSM":["GSM9631278","GSM9631277","GSM9631276","GSM9631275","GSM9631274","GSM9631273","GSM9631283","GSM9631272","GSM9631282","GSM9631281","GSM9631280","GSM9631279"],"GPL":["34284"],"GSE":["326441"],"taxon":["Homo sapiens"]}}