{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE310nnn/GSE310395/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":[" Other","Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310395"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"The early RNA decay factor ZC3H18 directs first intron splicing","description":"The splicing of pre-mRNA into mature mRNA is essential for proper gene expression. For multi-intronic transcripts, the Cap Binding Complex (CBC) has long been recognized as a critical facilitator of 1st intron splicing1–4, yet the underlying molecular mechanism remains elusive. The CBC is also involved in nuclear RNA decay. By binding the nascent RNA 5’cap during early RNA polymerase II (RNAPII) transcription, the CBC mediates the degradation of prematurely terminated transcripts (PTTs) notably by recruiting the Nuclear Exosome Targeting (NEXT) complex via the linker proteins ARS2 and ZC3H185–8. How the CBC orchestrates RNA degradation vs. processing is not understood. Here, we show that the interaction of ZC3H18 with three splicing factors, PRPF40A, PRPF4B and FNBP4, is critical for the global and ZC3H18-dependent stimulation of 1st intron splicing. Linking this unexpected function of ZC3H18 to the CBC, rapid ARS2 depletion phenocopies the splicing defects of ZC3H18 depletion and disrupting the physical link between ARS2 and ZC3H18 inactivates 1st intron splicing. Finally, although the CBC-ARS2-ZCH318 axis acts in both early RNA decay and 1st intron splicing, we demonstrate that binding of ZC3H18 with splicing factors is mutually exclusive with its binding to the NEXT component ZCCHC8. Collectively, our results explain cap-stimulated 1st intron splicing mechanistically and suggest that distinct splicing factors assign the nascent RNA to a productive pathway by displacing NEXT from ZC3H18.","dates":{"publication":"2026/09/29"},"accession":"GSE310395","cross_references":{"GSM":["GSM9295341","GSM9295342","GSM9295320","GSM9295340","GSM9295345","GSM9295323","GSM9295324","GSM9295346","GSM9295321","GSM9295343","GSM9295344","GSM9295322","GSM9754259","GSM9295338","GSM9295339","GSM9295336","GSM9295337","GSM9295318","GSM9295319","GSM9754257","GSM9295330","GSM9295352","GSM9295353","GSM9295331","GSM9295350","GSM9295351","GSM9295334","GSM9295335","GSM9754261","GSM9295332","GSM9295333","GSM9754260","GSM9295327","GSM9295349","GSM9754262","GSM9295328","GSM9295347","GSM9295325","GSM9754265","GSM9754264","GSM9295348","GSM9295326","GSM9754266","GSM9295329"],"GPL":["30173","28038","34281"],"GSE":["310395"],"taxon":["Homo sapiens"]}}