biostudies-literatureYin YNIGMS NIH HHS147-150https://www.ebi.ac.uk/biostudies/studies/S-EPMC12018070biostudies-literatureUnknown580(7801)Long noncoding RNAs (lncRNAs) and promoter- or enhancer-associated unstable transcripts locate preferentially to chromatin, where some regulate chromatin structure, transcription and RNA processing^1-13. Although several RNA sequences responsible for nuclear localization have been identified-such as repeats in the lncRNA Xist and Alu-like elements in long RNAs^14-16-how lncRNAs as a class are enriched at chromatin remains unknown. Here we describe a random, mutagenesis-coupled, high-throughput method that we name 'RNA elements for subcellular localization by sequencing' (mutREL-seq). Using this method, we discovered an RNA motif that recognizes the U1 small nuclear ribonucleoprotein (snRNP) and is essential for the localization of reporter RNAs to chromatin. Across the NatureU1 snRNP regulates chromatin retention of noncoding RNAs.PMC12018070R01 GM084089Yin YShan GLu JYShao WZhang QCHong YCui LZhang XTian BLi PShen XXu YfalseU1 snRNP regulates chromatin retention of noncoding RNAs.Long noncoding RNAs (lncRNAs) and promoter- or enhancer-associated unstable transcripts locate preferentially to chromatin, where some regulate chromatin structure, transcription and RNA processing^1-13. Although several RNA sequences responsible for nuclear localization have been identified-such as repeats in the lncRNA Xist and Alu-like elements in long RNAs^14-16-how lncRNAs as a class are enriched at chromatin remains unknown. Here we describe a random, mutagenesis-coupled, high-throughput method that we name 'RNA elements for subcellular localization by sequencing' (mutREL-seq). Using this method, we discovered an RNA motif that recognizes the U1 small nuclear ribonucleoprotein (snRNP) and is essential for the localization of reporter RNAs to chromatin. Across the 2020-01-01T00:00:00Z2020 Apr2026-06-01T11:00:53.975Z2025-07-09T03:04:51.883ZS-EPMC120180703223892410.1038/s41586-020-2105-3