GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296306/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296306GEOGSEfalseA genome-wide functional analysis of conserved intronic regions reveals essential roles for speckle-associated detained introns [RNAseq_candidates.RPE1]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.2026/06/18GSE296306GSM8968415GSM8968412GSM8968411GSM8968414GSM8968413GSM8968397GSM8968396GSM8968410GSM8968399GSM8968398GSM8968393GSM8968392GSM8968395GSM8968394GSM8968391GSM8968390GSM8968409GSM8968408GSM8968405GSM8968404GSM8968407GSM8968406GSM8968401GSM8968400GSM8968389GSM8968403GSM8968402GSM8968386GSM8968385GSM8968388GSM8968387GSM8968382GSM8968384GSM896838324676296306Homo sapiens