U1 snRNP regulates chromatin retention of noncoding RNAs

RNA subcellular localization often correlates with its function and regulation. For many long noncoding RNAs (lncRNAs) and some isoforms of coding genes, their transcripts are preferentially retained on the chromatin. However, the mechanisms controlling the chromatin retention of lncRNAs and mRNA transcripts remain largely unknown. We hypothesize that embedded RNA sequences and interacting proteins may be the cis and trans regulators governing RNA subcellular localization, respectively. To comprehensively identify the cis-regulatory elements of RNA transcript, here we have developed a high-throughput sequencing-based method named RNA elements for subcellular localization by sequencing (REL-seq). Using this method, we identified RNA sequences contribute to the chromatin retention of several transcripts. By combining REL-seq with random mutagenesis (mutREL-seq), we further narrowed down the key RNA motifs and residues in regulating their subcellular localization at base resolution. Finally, based on the RNA element we identified, we revealed and confirmed U1 snRNA targeting site contributes to RNA chromatin retention. Overall design: All RNA-seq(s) were designed to reveal differentially subcellular localized RNAs of RSLP library targeted genes.