GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE346nnn/GSE346485/primaryOK200TranscriptomicsHomo sapiens OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346485GEOGSEfalseCo-regulation of alternative splicing with transcription initiation and terminationNascent RNA processing requires coordination between transcription and splicing, yet the mechanisms underlying this coupling remain unclear. Here, we develop longPASS, a framework to identify and quantify transcription start site (TSS) and polyadenylation site (PAS) usage in long-read RNA sequencing data. In human cells, longPASS reveals thousands of TSS/PAS-associated alternative splicing events (TASEs) and reproducible links between TSS/PAS choice and exon inclusion across genetic perturbations, human tissues and individuals. Co-occurring pairs of TASE-exons and TASE-TSS/PASs tend to be proximal and show enriched RNA-RNA spatial interactions. Large-scale screening shows that RBMX specifically binds PAS-TASE pairs; RBMX depletion disrupts coordinated splicing and PAS usage, whereas canonical splicing-factor depletion has no significant effect. Manipulating RNA polymerase II elongation affects PAS-TASE coupling, with slower elongation increasing co-occurrence. Together, these findings establish genome-wide coupling between alternative splicing and TSS/PAS usage, implicate RBMX and polymerase II elongation in its regulation, and link this process to ageing.2026/09/09GSE346485GSM10034855GSM10034844GSM10034843GSM10034854GSM10034853GSM10034842GSM10034852GSM10034841GSM10034840GSM10034851GSM10034850GSM10034839GSM10034849GSM10034838GSM10034848GSM10034837GSM10034836GSM10034847GSM10034846GSM10034857GSM10034835GSM10034845GSM10034834GSM100348562616724106346485Homo sapiens