In plants, RNA silencing (RNA interference) is an efficient antiviral system, and therefore successful virus infection requires suppression of silencing. Although many viral silencing suppressors have been identified, the molecular basis of silencing suppression is poorly understood. It is proposed that various suppressors inhibit RNA silencing by targeting different steps. However, as double-stranded RNAs (dsRNAs) play key roles in silencing, it was speculated that dsRNA binding might be a general silencing suppression strategy. Indeed, it was shown that the related aureusvirus P14 and tombusvirus P19 suppressors are dsRNA-binding proteins. Interestingly, P14 is a size-independent dsRNA-binding protein, while P19 binds only 21-nucleotide ds-sRNAs (small dsRNAs having 2-nucleotide 3' overhangs), the specificity determinant of the silencing system. Much evidence supports the idea that P19 inhibits silencing by sequestering silencing-generated viral ds-sRNAs. In this study we wanted to test the hypothesis that dsRNA binding is a general silencing suppression strategy. Here we show that many plant viral silencing suppressors bind dsRNAs. Beet yellows virus Peanut P21, clump virus P15, Barley stripe mosaic virus gammaB, and Tobacco etch virus HC-Pro, like P19, bind ds-sRNAs size-selectively, while Turnip crinkle virus CP is a size-independent dsRNA-binding protein, which binds long dsRNAs as well as ds-sRNAs. We propose that size-selective ds-sRNA-binding suppressors inhibit silencing by sequestering viral ds-sRNAs, whereas size-independent dsRNA-binding suppressors inactivate silencing by sequestering long dsRNA precursors of viral sRNAs and/or by binding ds-sRNAs. The findings that many unrelated silencing suppressors bind dsRNA suggest that dsRNA binding is a general silencing suppression strategy which has evolved independently many times.
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http://dx.doi.org/10.1128/JVI.01963-05 | DOI Listing |
J Mol Neurosci
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Department of Neurosurgery, National Children's Medical Center (Shanghai), Children's Hospital of Fudan University, No.399 Wan Yuan Avenue, Minhang District, Shanghai, 201102, China.
Focal cortical dysplasia (FCD) II is a cortical malformation characterized by cortical architectural abnormalities, dysmorphic neurons, with or without balloon cells. Here, we systematically explored the pathophysiological role of the GATOR1 subunit NPRL3 variants including a novel mutation from iPSCs derived from one FCD II patient. Three FCD II children aged 0.
View Article and Find Full Text PDFAppl Microbiol Biotechnol
December 2024
Department of Life Science and Technology: Tokyo Kogyo Daigaku Seimei Rikogakuin Seimei Rikogakukei, Institute of Science Tokyo, 4259 Nagatsuta-Cho Midzeori-Ku, Yokohama, 226-8501, Japan.
Chiral diaryl alcohols, such as (4-chlorophenyl)(pyridin-2-yl)methanol, are important intermediates for pharmaceutical synthesis. However, using alcohol dehydrogenases (ADHs) in the asymmetric reduction of diaryl ketones to produce the corresponding alcohols is challenging due to steric hindrance in the substrate binding pockets of the enzymes. In this study, the steric hindrance of the ADH from Geotrichum candidum NBRC 4597 (G.
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December 2024
Exscientia, Oxford Science Park, Oxford, UK.
We introduce , an antibody variable domain diffusion model based on a general protein backbone diffusion framework, which was extended to handle multiple chains. Assessing the designability and novelty of the structures generated with our model, we find that produces highly designable antibodies that can contain novel binding regions. The backbone dihedral angles of sampled structures show good agreement with a reference antibody distribution.
View Article and Find Full Text PDFVet Sci
November 2024
Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou 225012, China.
Pigeon Newcastle disease (ND) is the most common viral infectious disease in the pigeon industry, caused by pigeon paramyxovirus type 1 (PPMV-1), a variant of chicken-origin Newcastle disease virus (NDV). Previous studies have identified significant amino acid differences between PPMV-1 and chicken-origin NDV at positions 347 and 349 in the hemagglutinin-neuraminidase (HN) protein, with PPMV-1 predominantly exhibiting glycine (G) at position 347 and glutamic acid (E) at position 349, while most chicken-origin NDVs show E at position 347 and aspartic acid (D) at position 349. However, the impact of these amino acid substitutions remains unclear.
View Article and Find Full Text PDFToxins (Basel)
December 2024
Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences-Campus Bellvitge, University of Barcelona, 08907 Barcelona, Spain.
Epsilon toxin (ETX) from is a pore-forming toxin (PFT) that crosses the blood-brain barrier and binds to myelin structures. In in vitro assays, ETX causes oligodendrocyte impairment, subsequently leading to demyelination. In fact, ETX has been associated with triggering multiple sclerosis.
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