GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296292/primary200OKOther synthetic constructHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296292GEOGSEfalseA genome-wide functional analysis of conserved intronic regions reveals essential roles for speckle-associated detained introns [CHyMErA]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.2026/06/18GSE296292GSM8968159GSM8968158GSM8968177GSM8968155GSM8968154GSM8968176GSM8968157GSM8968179GSM8968178GSM8968156GSM8968151GSM8968173GSM8968172GSM8968150GSM8968175GSM8968153GSM8968174GSM8968152GSM8968171GSM8968170GSM8968148GSM8968169GSM8968147GSM8968149GSM8968166GSM8968144GSM8968143GSM8968165GSM8968146GSM8968168GSM8968167GSM8968145GSM8968162GSM8968161GSM8968164GSM8968163GSM8968180GSM8968160GSM8968182GSM89681812467626526296292 synthetic constructHomo sapiens