Phase Separation of Heterogeneous Nuclear Ribonucleoprotein A1 upon Specific RNA-Binding Observed by Magnetic Resonance. 2022

Irina Ritsch, and Elisabeth Lehmann, and Leonidas Emmanouilidis, and Maxim Yulikov, and Frédéric Allain, and Gunnar Jeschke
Laboratory of Physical Chemistry, Department of Chemistry and Applied Bioscience, ETH Zurich, Vladimir-Prelog-Weg 2, 8093, Zürich, Switzerland.

Interaction of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) with specific single-stranded RNA and its relation to liquid-liquid phase separation (LLPS) were studied in vitro by magnetic resonance based on site-directed spin labelling. An ensemble model of dispersed hnRNP A1 in the absence of RNA was derived from distance distributions between spin labelled sites and small angle X-ray scattering. This model revealed a compact state of the low-complexity domain and its interaction with the RNA recognition motifs. Paramagnetic relaxation enhancement NMR spectroscopy confirmed this interaction. Addition of RNA to dispersed hnRNP A1 induced liquid-droplet formation. Such LLPS depended on RNA concentration and sequence, with continuous wave EPR spectroscopy showing an influence of RNA point mutations on local protein dynamics. We propose that an interplay of sequence-specific RNA binding and LLPS contributes to regulation of specific RNA segregation during stress response.

UI MeSH Term Description Entries
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D000076245 Heterogeneous Nuclear Ribonucleoprotein A1 A heterogeneous ribonucleoprotein that contains an RNA-BINDING MOTIF and has poly(ADP)ribose-binding capability. It functions in the packaging of pre-mRNA into hnRNP particles for export to the cytoplasm and may play a role in RNA SPLICING site selection. A1 HnRNP,hnRNP A1,hnRNP A1 Protein,hnRNP Protein A1
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D034481 Heterogeneous-Nuclear Ribonucleoprotein Group A-B A class of closely related heterogeneous-nuclear ribonucleoproteins of approximately 34-40 kDa in size. Although they are generally found in the nucleoplasm, they also shuttle between the nucleus and the cytoplasm. Members of this class have been found to have a role in mRNA transport, telomere biogenesis and RNA SPLICING. hnRNP A-B Proteins,A-B Family hnRNP Proteins,Heterogeneous Nuclear Ribonucleoprotein A2-B1,Type A-B hnRNP Proteins,hnRNP A2-B1,A B Family hnRNP Proteins,Heterogeneous Nuclear Ribonucleoprotein A2 B1,Heterogeneous Nuclear Ribonucleoprotein Group A B,Type A B hnRNP Proteins,hnRNP A B Proteins

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