GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296299/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296299GEOGSEfalseA genome-wide functional analysis of conserved intronic regions reveals essential roles for speckle-associated detained introns [RNAseq_candidates.HAP1]Thousands of human introns harbour extended regions of high evolutionarily conservation that have not been previously characterized. A survey of these sequences reveals that they are associated with intron retention and enriched in genes that function in RNA processing, chromatin remodelling and neuronal biology. Using a dual CRISPR-Cas editing approach, we targeted 2,600 of these regions for deletion and observe that a subset of these perturbations affectaffects cell growth. Many of these ‘fitness’ sequences affect intron retention and or expression levels of their host genes. Deletions in nuclear speckle-associated retained introns in the FNBP4 and DDX5 genes are further linked to downstream effects on cell growth-related genes and intron retention, respectively. The DDX5 deletion additionally results in the accumulation of R-loops overlapping first introns in speckle-proximal genes. Overall, the results highlight multifactetedmultifaceted, critical roles of highly conserved intronic sequences in the control of gene regulation, R-loop resolution and cell growth.2026/06/18GSE296299GSM8968312GSM8968279GSM8968298GSM8968276GSM8968297GSM8968275GSM8968278GSM8968311GSM8968277GSM8968310GSM8968299GSM8968294GSM8968272GSM8968293GSM8968271GSM8968274GSM8968296GSM8968295GSM8968273GSM8968290GSM8968292GSM8968270GSM8968291GSM8968309GSM8968306GSM8968305GSM8968308GSM8968307GSM8968269GSM8968302GSM8968301GSM8968304GSM8968303GSM8968287GSM8968286GSM8968300GSM8968289GSM8968288GSM8968283GSM8968282GSM8968285GSM8968284GSM8968281GSM896828024676296299Homo sapiens