GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE341nnn/GSE341315/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE341315GEOGSEfalseStructural analysis of chemically probed pre-mRNA structure using RADISPre-mRNA secondary structure can modulate the regulatory function of intronic sequences by masking or exposing splice-site signals and altering the accessibility of other features. Yet experimentally grounded structural models for human pre-mRNAs have been largely restricted to experimentally grounded structural models for human pre-mRNAs have been largely restricted to splice-site-proximal regions, leaving the deep intronic regions, where ~70% of intronic disease-causing variants reside, almost entirely unmapped. We developed RADIS (Reactivity Analysis of Deep and Intergenic RNA Structure), a strategy that yields strand-resolved chemical probing reactivity profiles across entire intron-rich loci by creating tiled arrays of RNAs that comprehensively span long genomic distances. This approach removes the abundance and locus-specificity constraints that otherwise limit pre-mRNA probing approaches. RADIS recovers known E. coli ribosomal RNA architectures and yields high-correlation in-cell dimethyl sulfate (DMS)-MaP reactivities at representative splice sites (r = 0.87–0.90). RADIS-constrained folding of 109 5′ and 88 3′ splice sites uncovers an inverse relationship between base-pairing across the spliceosome footprint and splice-site strength, and partitions 81 branchpoints into three structural classes. Across 233 full-length Alu elements, sense Alu RNAs are more structured than antisense elements, and both partition into strand- and lineage-dependent structural classes. RADIS provides a generalizable route to experimentally grounded interpretation at intron-rich disease-associated and intergenic loci, complementing sequence-based variant-effect predictors.2026/09/13GSE341315GSM9903630GSM9903639GSM9903635GSM9903636GSM9903637GSM9903638GSM9903631GSM9903632GSM9903633GSM9903634GSM9903640GSM9903641GSM9903606GSM9903607GSM9903608GSM9903609GSM9903646GSM9903647GSM9903604GSM9903648GSM9903649GSM9903605GSM9903642GSM9903643GSM9903644GSM9903645GSM9903650GSM9903651GSM9903652GSM9903617GSM9903618GSM9903619GSM9903613GSM9903657GSM9903658GSM9903614GSM9903615GSM9903659GSM9903616GSM9903653GSM9903610GSM9903654GSM9903655GSM9903611GSM9903612GSM9903656GSM9903660GSM9903661GSM9903662GSM9903663GSM9903628GSM9903629GSM9903624GSM9903625GSM9903626GSM9903627GSM9903620GSM9903664GSM9903621GSM9903665GSM9903666GSM9903622GSM99036233088215520341315Homo sapiens