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The sensing of nucleic acids by receptors of the innate immune system is a key component of antimicrobial immunity. RNA:DNA hybrids, as essential intracellular replication intermediates generated during infection, could therefore represent a class of previously uncharacterised pathogen-associated molecular patterns sensed by pattern recognition receptors. Here we establish that RNA:DNA hybrids containing viral-derived sequences efficiently induce pro-inflammatory cytokine and antiviral type I interferon production in dendritic cells. We demonstrate that MyD88-dependent signalling is essential for this cytokine response and identify TLR9 as a specific sensor of RNA:DNA hybrids. Hybrids therefore represent a novel molecular pattern sensed by the innate immune system and so could play an important role in host response to viruses and the pathogenesis of autoimmune disease.
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http://dx.doi.org/10.1002/embj.201386117 | DOI Listing |
Adv Sci (Weinh)
September 2025
Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, 310022, China.
Asthma is a chronic inflammatory respiratory disease influenced by genetic and environmental factors. Emerging evidence suggests that microplastics and nanoplastics (NPs) pose significant health risks. When inhaled, these tiny particles can accumulate in the lungs, triggering inflammation, oxidative stress, and other disruptions in pulmonary function.
View Article and Find Full Text PDFNat Commun
August 2025
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
Conventional genome editing tools rely on DNA double-strand breaks (DSBs) and host recombination proteins to achieve large insertions, resulting in heterogeneous mixtures of undesirable outcomes. We recently leveraged a type I-F CRISPR-associated transposase, PseCAST, for DSB-free DNA integration in human cells, albeit at low efficiencies; multiple lines of evidence suggest DNA binding may be a bottleneck for higher efficiencies. Here we report structural determinants of DNA recognition by the PseCAST QCascade complex using single-particle cryogenic electron microscopy (cryoEM), revealing subtype-specific interactions and RNA-DNA heteroduplex features.
View Article and Find Full Text PDFNucleic Acids Res
August 2025
Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, Trojdena 4, Warsaw 02-109, Poland.
R-loops are nucleic acid structures composed of an RNA/DNA hybrid and a displaced single-stranded DNA that form during transcription. Their defective processing has been implicated in genome instability, which is associated with severe human diseases. Despite their biological significance, the mechanisms regulating R-loops remain incompletely understood, underscoring the need for improved tools to accurately map R-loops across the genome.
View Article and Find Full Text PDFCancer Manag Res
August 2025
Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Background: R-loops, RNA-DNA hybrid structures, play essential roles in maintaining genomic stability and regulating transcription. This study aims to identify key R-loop regulatory genes as prognostic markers for LUAD and explore their associations with immunotherapy response and drug sensitivity, supporting personalized treatment strategies.
Methods: We integrated 1771 R-loops genes with differentially expressed genes in LUAD.
Front Genet
July 2025
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Objective: Single-cell transcriptome sequencing is a powerful tool for investigating cellular diversity in normal development and disease. However, prevalent methods predominantly employ 3'-end sequencing of transcripts, limiting the analysis of alternative splicing and other post-transcriptional processes. While full-length single-cell transcriptome sequencing methods, such as Smart-seq, offer more comprehensive information, but are restricted by low-throughput.
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