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RNA-Puzzles is a collective endeavor dedicated to the advancement and improvement of RNA three-dimensional structure prediction. With agreement from structural biologists, RNA structures are predicted by modeling groups before publication of the experimental structures. We report a large-scale set of predictions by 18 groups for 23 RNA-Puzzles: 4 RNA elements, 2 Aptamers, 4 Viral elements, 5 Ribozymes and 8 Riboswitches. We describe automatic assessment protocols for comparisons between prediction and experiment. Our analyses reveal some critical steps to be overcome to achieve good accuracy in modeling RNA structures: identification of helix-forming pairs and of non-Watson-Crick modules, correct coaxial stacking between helices and avoidance of entanglements. Three of the top four modeling groups in this round also ranked among the top four in the CASP15 contest.
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http://dx.doi.org/10.1038/s41592-024-02543-9 | DOI Listing |
Cell Res
September 2025
Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
The pre-dimerization of endosome-localized RNA sensor Toll-like receptor 3 (TLR3) is required for its innate recognition, yet how TLR3 pre-dimers are formed and precisely primed for innate activation remains unclear. Here, we demonstrate that endosome-localized self RNA Rmrp directly binds to TLR3 and induces TLR3 dimerization in the early endosome but does not interact with endosome-localized TLR7, TLR8, TLR9 or cytoplasmic RNA sensor RIG-I under homeostatic conditions. Cryo-EM structure of Rmrp-TLR3 complex reveals a novel lapped conformation of TLR3 dimer engaged by Rmrp, which is distinct from the activation mechanism by dsRNA and the specific structural feature at the 3'-end of Rmrp is critical for its functional interaction with TLR3.
View Article and Find Full Text PDFBiochimie
September 2025
Immunopathology and Viral Reservoir Unit, National Center of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; Biomedical Research Center Network in Infectious Diseases (CIBERINFEC), Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
TLR8 and TLR9 are innate immune receptors belonging to the TLR family that are essential for viral recognition and early immune activation. Their dysfunction is linked to increased susceptibility to infections. TLR8 detects viral single- and double-stranded RNA, while TLR9 recognizes viral DNA molecules with CpG motifs.
View Article and Find Full Text PDFPhytopathology
September 2025
Shandong Agricultural University, College of Plant Protection, Tai'an, Shandong, China;
Wheat yellow mosaic virus (WYMV) is the main cause of wheat yellow mosaic disease. Although its regulation of protein translation and interactions with host proteins are well-studied, independent regulation of the virus genome is poorly understood. This study performed in vitro experiments investigating replication regulation by the 5' UTR and 3' UTR of WYMV RNA2.
View Article and Find Full Text PDFBiophys J
September 2025
Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, 4401 University Drive, Lethbridge, AB, T1K 3M4, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton T6G 2E1, Alberta, Canada; Department of Microbiology, Immunology
The dengue virus (DENV) poses a significant threat to human health, accounting for approximately 400 million infections each year. Its genome features a circular structure that facilitates replication through long-range RNA-RNA interactions, utilizing cyclization sequences located in the untranslated regions (UTRs). To gain new insights into the organization of the DENV genome, we purified the 5' and 3' UTRs of DENV in vitro and examined their structural and binding properties using various biophysical techniques combined with computational methods.
View Article and Find Full Text PDFAnal Biochem
September 2025
School of Computer Science and Engineering, Southeast University, Nanjing 210000, China.
In the complex process of gene expression and regulation, RNA-binding proteins occupy a pivotal position for RNA. Accurate prediction of RNA-protein binding sites can help researchers better understand RNA-binding proteins and their related mechanisms. And prediction techniques based on machine learning algorithms are both cost-effective and efficient in identifying these binding sites.
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