U1 snRNP regulates chromatin retention of noncoding RNAs

Abstract

Thousands of noncoding transcripts exist in mammalian genomes, and they preferentially localize to chromatin. Here, to identify cis-regulatory elements that control RNA-chromatin association, we developed a high-throughput method named RNA element for subcellular localization by sequencing (REL-seq). Coupling REL-seq with random mutagenesis (mutREL-seq), we discovered a key 7-nt U1 recognition motif in chromatin-enriched RNA elements. Reporter assays indicated a direct role for U1 snRNP recognition in regulating RNA-chromatin localization. Globally, U1 motifs and U1 binding are strongly enriched in long noncoding RNA (lncRNA) transcripts. Inhibition of U1 snRNA, and of U2 to a lesser degree, led to global reduction in chromatin association of hundreds of lncRNAs.For promoter-and enhancer-associated noncoding RNAs, U1 binds to their genomic neighborhoods, and their chromatin association depends on both U1 and U2 snRNAs. These findings reveal that U1 snRNP, perhaps together with the splicing machinery, acts widely to promote the chromatin association of noncoding transcripts.

Long non-coding RNAs in plants: emerging modulators of gene activity in development and stress responses

“…Bazin et al 2017 ; Hsu et al 2016 ), and some of these lncRNAs could eventually contribute to biogenesis of small peptides. A set of nuclear lncRNAs are bound by chromatin, and this localization can be stabilized by U1 snRNP (U1 small nuclear ribonucleoprotein particle) in mammals (Yin et al 2020 ). Chromatin-associated lncRNAs potentially influence TF binding or the functionality of enhancers (Shlyueva et al 2014 ).…”

In vivodiscovery of RNA proximal proteins in human cells via proximity-dependent biotinylation

“…U1 RPPs also included previously reported U1 interactor RNA polymerase II (Spiluttini et al, 2010; Yu and Reed, 2015) (Figure 3F), which is required for a noncanonical role of U1 in chromatin retention of ncRNAs (Yin et al, 2020). Moreover, U1 RPL retrieved proteins involved in chromatin remodeling, DNA modification, histone modification, and transcription (Table S1), which could be regulated by chromatin-associated ncRNAs (Huang et al, 2020; Li and Fu, 2019).…”

Cis-acting lnc-eRNA SEELA directly binds histone H4 to promote histone recognition and leukemia progression

“…Therefore, affinity interactions to chromatin-binding proteins cannot fully account for the specific localization of lncRNAs to precise loci. Another explanation was recently proposed: a study reported that the U1 snRNP interacts with transcriptionally engaged POL II to tether and mobilize lncRNAs to chromatin in a transcription-dependent manner [ 53 ]. In this study, we demonstrated that lnc-eRNAs bound histone H4, which seemed to control the chromatin retention and cis regulation function of lnc-eRNAs.…”