RNA molecules display distinctive organization at nuclear speckles

• Published in: iScience 2024-05, Vol.27 (5), p.109603, Article 109603
• Main Authors: Paul, Sneha, Arias, Mauricio A., Wen, Li, Liao, Susan E., Zhang, Jiacheng, Wang, Xiaoshu, Regev, Oded, Fei, Jingyi
• Format: Article
• Language: English
• Subjects: Molecular interaction; Molecular physiology; Nucleic acids; Properties of biomolecules
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.109603

RNA molecules often play critical roles in assisting the formation of membraneless organelles in eukaryotic cells. Yet, little is known about the organization of RNAs within membraneless organelles. Here, using super-resolution imaging and nuclear speckles as a model system, we demonstrate that different sequence domains of RNA transcripts exhibit differential spatial distributions within speckles. Specifically, we image transcripts containing a region enriched in binding motifs of serine/arginine-rich (SR) proteins and another region enriched in binding motifs of heterogeneous nuclear ribonucleoproteins (hnRNPs). We show that these transcripts localize to the outer shell of speckles, with the SR motif-rich region localizing closer to the speckle center relative to the hnRNP motif-rich region. Further, we identify that this intra-speckle RNA organization is driven by the strength of RNA-protein interactions inside and outside speckles. Our results hint at novel functional roles of nuclear speckles and likely other membraneless organelles in organizing RNA substrates for biochemical reactions. [Display omitted] •Regions in RNA exhibit distinct positioning and orientation at nuclear speckles•SR motif-enriched regions localize closer to speckle center than hnRNP ones•RNA organization is driven by interactions with proteins inside and outside speckle Nucleic acids; Properties of biomolecules; Molecular physiology; Molecular interaction