GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE319nnn/GSE319926/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319926GEOGSEfalseSERIPH: A Two-Step Extraction Protocol for Selective Enrichment of Semi-Extractable RNAsConventional RNA extraction with acid guanidinium thiocyanate–phenol–chloroform (AGPC) reagents incompletely recovers a subset of transcripts, termed semi-extractable RNAs (seRNAs). This underrepresented RNA population includes architectural RNAs (arcRNAs), which scaffold membraneless organelles, as well as stress-induced downstream-of-gene readthrough transcripts (DoGs). Although our previously developed “improved” AGPC protocol incorporating physical disruption enhances seRNA recovery, it also co-extracts abundant, readily extractable RNAs, yielding mixed populations that hinder precise characterization of seRNAs. Here, we present SERIPH (Semi-Extractable RNA Isolation from the InterPHase), a simple two-step protocol that selectively enriches seRNAs by separating them from readily extractable RNA species. By depleting abundant extractable RNAs, SERIPH increases detection sensitivity, enabling the capture of weakly semi-extractable transcripts, including those of low abundance, that were overlooked by previous approaches. This increased sensitivity expands the detectable seRNA repertoire and reveals a broader genomic extent of DoG transcription than previously appreciated. Together, SERIPH provides a robust framework for high-resolution analysis of seRNA populations, advancing studies of RNA processing, transcriptional regulation, and RNA-mediated nuclear organization in stress responses and disease2026/06/27GSE319926GSM9529444GSM9529445GSM9529446GSM9529447GSM9529436GSM9529437GSM9529448GSM9529438GSM9529449GSM9529439GSM9529450GSM9529440GSM9529451GSM9529441GSM9529442GSM952944334281319926Homo sapiens[42350076]