Processing of RNA is a key regulatory mechanism for all living systems. We recently discovered a novel family of endoribonucleases that is conserved across all bacteria. Here, using crystallography, cryo-EM microscopy, biochemical, biophysical, and mass spectrometry techniques, we are able to shed light on a novel RNA cleavage mechanism in bacteria. We show that YicC, the prototypical member of this family, forms a hexameric channel that closes down on a 26-mer RNA substrate, and find that it cleaves across an RNA hairpin to generate several short fragments.
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http://dx.doi.org/10.21203/rs.3.rs-3788707/v1 | DOI Listing |
J Hepatol
January 2025
Department of Biomedicine, University of Basel, Switzerland; University Centre for Gastrointestinal and Liver Disease Basel, Switzerland. Electronic address:
Background & Aims: Infectious complications determine the prognosis of cirrhosis patients. Their infection susceptibility relates to the development of immuneparesis, a complex interplay of different immunosuppressive cells and soluble factors. Mechanisms underlying the dynamics of immuneparesis of innate immunity remain inconclusive.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Research Center for Life Sciences Computing, Zhejiang Lab, Kechuang Avenue, Yuhang District, Hangzhou, Zhejiang, 311121, China.
The CRISPR-derived endoribonuclease Csy4 is a popular tool for controlling transgene expression in various therapeutically relevant settings, but adverse effects potentially arising from non-specific RNA cleavage remains largely unexplored. Here, we report a split-Csy4 architecture that was carefully optimized for in vivo usage. First, we separated Csy4 into two independent protein moieties whose full catalytic activity can be restored via various constitutive or conditional protein dimerization systems.
View Article and Find Full Text PDFNarra J
December 2024
Animal Research Facilities, Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) offers a robust approach for genome manipulation, particularly in cancer therapy. Given its high expression in triple-negative breast cancer (TNBC), targeting with CRISPR/Cas9 holds promise as a therapeutic strategy. The aim of this study was to design specific single guide ribonucleic acid (sgRNA) for CRISPR/Cas9 to permanently knock out the gene, exploring its potential as a therapeutic approach in breast cancer while addressing potential off-target effects.
View Article and Find Full Text PDFNature
January 2025
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
Argonaute proteins are categorized into AGO and PIWI clades. Across most animal species, AGO-clade proteins are widely expressed in various cell types, and regulate normal gene expression. By contrast, PIWI-clade proteins predominantly function during gametogenesis to suppress transposons and ensure fertility.
View Article and Find Full Text PDFNat Commun
January 2025
Laboratory of Pathogens and Host Immunity, UMR 5294 CNRS, UA15 INSERM, Université de Montpellier, Montpellier, 34095, France.
Programmed-cell death is an antimicrobial defense mechanism that promotes clearance of intracellular pathogens. Toxoplasma counteracts host immune defenses by secreting effector proteins into host cells; however, how the parasite evades lytic cell death and the effectors involved remain poorly characterized. We identified ROP55, a rhoptry protein that promotes parasite survival by preventing lytic cell death in absence of IFN-γ stimulation.
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