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RNA is the key player in many cellular processes such as signal transduction, replication, transport, cell division, transcription, and translation. These diverse functions are accomplished through interactions of RNA with proteins. However, protein-RNA interactions are still poorly derstood in contrast to protein-protein and protein-DNA interactions. This knowledge gap can be attributed to the limited availability of protein-RNA structures along with the experimental difficulties in studying these complexes. Recent progress in computational resources has expanded the number of tools available for studying protein-RNA interactions at various molecular levels. These include tools for predicting interacting residues from primary sequences, modelling of protein-RNA complexes, predicting hotspots in these complexes and insights into derstanding in the dynamics of their interactions. Each of these tools has its strengths and limitations, which makes it significant to select an optimal approach for the question of interest. Here we present a mini review of computational tools to study different aspects of protein-RNA interactions, with focus on overall application, development of the field and the future perspectives.
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http://dx.doi.org/10.3389/fmolb.2022.954926 | DOI Listing |
Nat Biotechnol
September 2025
Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA, USA.
RNA-protein interactions critically regulate gene expression and cellular processes, yet their comprehensive mapping remains challenging due to their structural diversity. We introduce PRIM-seq (protein-RNA interaction mapping by sequencing), a method for concurrent de novo identification of RNA-binding proteins and their associated RNAs. PRIM-seq generates unique chimeric DNA sequences by proximity ligation of RNAs with protein-linked DNA barcodes, which are subsequently decoded through sequencing.
View Article and Find Full Text PDFJ Chem Phys
September 2025
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
We study how protein condensates respond to a site of active RNA transcription (i.e., a gene promoter) due to electrostatic protein-RNA interactions.
View Article and Find Full Text PDFJ Phys Chem B
September 2025
Hefei National Research Center for Physical Sciences at the Microscale and Key Laboratory of Precision and Intelligent Chemistry, Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.
Multivalent protein-protein interactions play essential roles in mediating liquid-liquid phase separation (LLPS) that drives biomolecular condensate formation. Here, we systematically investigate how the spatial distribution and relative size of protein binding domains (PBDs) would influence LLPS in a mixture of spherical proteins and RNA single strands by using a patchy-particle polymer model, wherein each protein contains a fixed number of PBDs on the surface distributed closely or sparsely. Intriguingly, we find that LLPS behavior exhibits a nontrivial dependence on the cooperative interplay between PBD distribution and protein size: while sparsely distributed PBDs are more favorable to LLPS for small proteins, closely packed PBDs facilitate LLPS for larger counterparts.
View Article and Find Full Text PDFMagn Reson Chem
September 2025
Transcription Regulation Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Epithelial splicing regulatory protein 2 (ESRP2) plays a pivotal role in alternative splicing regulation, particularly in maintaining epithelial cell identity and suppressing epithelial-to-mesenchymal transition (EMT). Despite its biological significance, the structural basis for its RNA-binding specificity remains poorly understood. In this study, we report the solution structure and RNA-binding properties of the RNA Recognition Motif (RRM3) of human ESRP2 using an integrative approach combining nuclear magnetic resonance (NMR) spectroscopy, ITC, molecular docking, and MD simulations.
View Article and Find Full Text PDFBiomacromolecules
September 2025
Department of Chemical Engineering, Columbia University, New York, New York 10027, United States.
Biomolecular condensates (BMCs) are central to subcellular organization, influencing processes from RNA metabolism to the stress response and amyloid pathologies. Despite their near ubiquity, we still do not fully understand how the primary sequence of biomolecules influences the formation and dynamics of condensates. Here, we examine how cationic amino acid identity shapes the properties of protein-RNA coacervates.
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