GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296298/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296298GEOGSEfalseA genome-wide functional analysis of conserved intronic regions reveals essential roles for speckle-associated detained introns [RNAseq_CHX]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.2026/06/18GSE296298GSM8968265GSM8968264GSM8968267GSM8968266GSM8968261GSM8968260GSM8968263GSM8968262GSM8968258GSM8968268GSM8968257GSM896825924676296298Homo sapiens