2,144 results match your criteria silencing machinery

Human DICER helicase domain recruits PKR and modulates its antiviral activity.

PLoS Pathog 2021 May 13;17(5):e1009549. Epub 2021 May 13.

Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, Strasbourg, France.

The antiviral innate immune response mainly involves type I interferon (IFN) in mammalian cells. The contribution of the RNA silencing machinery remains to be established, but several recent studies indicate that the ribonuclease DICER can generate viral siRNAs in specific conditions. It has also been proposed that type I IFN and RNA silencing could be mutually exclusive antiviral responses. Read More

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Beyond ribose and phosphate: Selected nucleic acid modifications for structure-function investigations and therapeutic applications.

Beilstein J Org Chem 2021 28;17:908-931. Epub 2021 Apr 28.

Department of Chemistry and Biochemistry, Concordia University, Montréal, Québec H4B 1R6, Canada.

Over the past 25 years, the acceleration of achievements in the development of oligonucleotide-based therapeutics has resulted in numerous new drugs making it to the market for the treatment of various diseases. Oligonucleotides with alterations to their scaffold, prepared with modified nucleosides and solid-phase synthesis, have yielded molecules with interesting biophysical properties that bind to their targets and are tolerated by the cellular machinery to elicit a therapeutic outcome. Structural techniques, such as crystallography, have provided insights to rationalize numerous properties including binding affinity, nuclease stability, and trends observed in the gene silencing. Read More

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Loss of EZH2-like or SU(VAR)3-9-like proteins causes simultaneous perturbations in H3K27 and H3K9 tri-methylation and associated developmental defects in the fungus Podospora anserina.

Epigenetics Chromatin 2021 May 7;14(1):22. Epub 2021 May 7.

Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, 91198, Gif-sur-Yvette, France.

Background: Selective gene silencing is key to development. It is generally accepted that H3K27me3-enriched heterochromatin maintains transcriptional repression established during early development and regulates cell fate. Conversely, H3K9me3-enriched heterochromatin prevents differentiation but constitutes protection against transposable elements. Read More

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Fol-milR1, a pathogenicity factor of Fusarium oxysporum, confers tomato wilt disease resistance by impairing host immune responses.

New Phytol 2021 May 7. Epub 2021 May 7.

College of Horticulture and Plant Protection, Yangzhou University, Yangzhou, JS, 225009, China.

Although miRNAs are well known to play crucial roles in multiple biological processes, there is currently no evidence indicating milRNAs from Fusarium oxysporum f.sp. lycopersici (Fol) interfere with tomato resistance during infection. Read More

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LIMIT is an immunogenic lncRNA in cancer immunity and immunotherapy.

Nat Cell Biol 2021 May 6;23(5):526-537. Epub 2021 May 6.

Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Major histocompatibility complex-I (MHC-I) presents tumour antigens to CD8 T cells and triggers anti-tumour immunity. Humans may have 30,000-60,000 long noncoding RNAs (lncRNAs). However, it remains poorly understood whether lncRNAs affect tumour immunity. Read More

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CRISPR interference and its applications.

Prog Mol Biol Transl Sci 2021 12;180:123-140. Epub 2021 Feb 12.

Department of Biochemistry and Synthetic Metabolism, Max-Planck Institute for Terrestrial Microbiology, Marburg, Germany. Electronic address:

Sequence-specific control of gene expression is a powerful tool for identifying and studying gene functions and cellular processes. CRISPR interference (CRISPRi) is an RNA-based method for highly specific silencing of the transcription in prokaryotic or eukaryotic cells. The typical CRISPRi system is a type II CRISPR (clustered regularly interspaced palindromic repeats) machinery of Streptococcus pyogenes. Read More

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February 2021

Nanoparticles as Drug Delivery Systems of RNAi in Cancer Therapy.

Molecules 2021 Apr 19;26(8). Epub 2021 Apr 19.

School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China.

RNA interference (RNAi) can mediate gene-silencing by knocking down the expression of a target gene via cellular machinery with much higher efficiency in contrast to other antisense-based approaches which represents an emerging therapeutic strategy for combating cancer. Distinct characters of nanoparticles, such as distinctive size, are fundamental for the efficient delivery of RNAi therapeutics, allowing for higher targeting and safety. In this review, we present the mechanism of RNAi and briefly describe the hurdles and concerns of RNAi as a cancer treatment approach in systemic delivery. Read More

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Transcriptional silencing of ALDH2 confers a dependency on Fanconi anemia proteins in acute myeloid leukemia.

Cancer Discov 2021 Apr 23. Epub 2021 Apr 23.

Cold Spring Harbor Laboratory

Hundreds of genes become aberrantly silenced in acute myeloid leukemia (AML), with most of these epigenetic changes being of unknown functional consequence. Here, we demonstrate how gene silencing can lead to an acquired dependency on the DNA repair machinery in AML. We make this observation by profiling the essentiality of the ubiquitination machinery in cancer cell lines using domain-focused CRISPR screening, which revealed Fanconi anemia (FA) proteins UBE2T and FANCL as unique dependencies in AML. Read More

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Genome-wide identification, evolutionary relationship and expression analysis of AGO, DCL and RDR family genes in tea.

Sci Rep 2021 Apr 21;11(1):8679. Epub 2021 Apr 21.

Department of Botany, Gauhati University, Jalukbari, Guwahati, Assam, 781014, India.

Three gene families in plants viz. Argonaute (AGOs), Dicer-like (DCLs) and RNA dependent RNA polymerase (RDRs) constitute the core components of small RNA mediated gene silencing machinery. The present study endeavours to identify members of these gene families in tea and to investigate their expression patterns in different tissues and various stress regimes. Read More

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and Loss Induces an Immune Response in Zebrafish Livers Due to Viral Mimicry by Transposable Elements.

Front Immunol 2021 29;12:627926. Epub 2021 Mar 29.

Program in Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.

Activation of transposable elements (TEs) can cause cellular damage. Cytoplasmic nucleic acid sensing pathways evolved to detect pathogens, but can also serve to cull cells with inappropriate TE activation as TEs can be viral mimetics. Epigenetic silencing of TEs is mediated in part by DNA methylation, but it is not clear if TE activation or the immune system contribute to the cellular damage caused by loss of DNA methylation. Read More

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Nanobody-Dependent Delocalization of Endocytic Machinery in Root Cells Dampens Their Internalization Capacity.

Front Plant Sci 2021 19;12:538580. Epub 2021 Mar 19.

Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.

Plant cells perceive and adapt to an ever-changing environment by modifying their plasma membrane (PM) proteome. Whereas secretion deposits new integral membrane proteins, internalization by endocytosis removes membrane proteins and associated ligands, largely with the aid of adaptor protein (AP) complexes and the scaffolding molecule clathrin. Two AP complexes function in clathrin-mediated endocytosis at the PM in plant cells, the heterotetrameric AP-2 complex and the hetero-octameric TPLATE complex (TPC). Read More

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Gene Expression Analysis of Induced (Sharka) Resistance in Peach () by Almond () Grafting.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Department of Plant Breeding, CEBAS-CSIC, P.O. Box 164, 30100 Murcia, Spain.

No natural sources of resistance to (PPV, sharka disease) have been identified in peach. However, previous studies have demonstrated that grafting a "Garrigues" almond scion onto "GF305" peach rootstock seedlings heavily infected with PPV can progressively reduce disease symptoms and virus accumulation. Furthermore, grafting a "Garrigues" scion onto the "GF305" rootstock has been shown to completely prevent virus infection. Read More

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Variability, Functions and Interactions of Plant Virus Movement Proteins: What Do We Know So Far?

Microorganisms 2021 Mar 27;9(4). Epub 2021 Mar 27.

Department of Plant Molecular Biology, University of Delhi South Campus, New Delhi 110021, India.

Of the various proteins encoded by plant viruses, one of the most interesting is the movement protein (MP). MPs are unique to plant viruses and show surprising structural and functional variability while maintaining their core function, which is to facilitate the intercellular transport of viruses or viral nucleoprotein complexes. MPs interact with components of the intercellular channels, the plasmodesmata (PD), modifying their size exclusion limits and thus allowing larger particles, including virions, to pass through. Read More

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The Yin and Yang of Histone Marks in Transcription.

Annu Rev Genomics Hum Genet 2021 Mar 29. Epub 2021 Mar 29.

Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; email:

Nucleosomes wrap DNA and impede access for the machinery of transcription. The core histones that constitute nucleosomes are subject to a diversity of posttranslational modifications, or marks, that impact the transcription of genes. Their functions have sometimes been difficult to infer because the enzymes that write and read them are complex, multifunctional proteins. Read More

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TUFM is involved in Alzheimer's disease-like pathologies that are associated with ROS.

FASEB J 2021 May;35(5):e21445

Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, China.

Mitochondrial Tu translation elongation factor (TUFM or EF-Tu) is part of the mitochondrial translation machinery. It is reported that TUFM expression is reduced in the brain of Alzheimer's disease (AD), suggesting that TUFM might play a role in the pathophysiology. In this study, we found that TUFM protein level was decreased in the hippocampus and cortex especially in the aged APP/PS1 mice, an animal model of AD. Read More

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Leishmania (V.) braziliensis infection promotes macrophage autophagy by a LC3B-dependent and BECLIN1-independent mechanism.

Acta Trop 2021 Jun 18;218:105890. Epub 2021 Mar 18.

Laboratory of Cellular Biology, IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil.

Leishmania (Viannia) braziliensis is one of the main etiological agents of tegumentary leishmaniasis in Latin America. The establishment of a successful infection in host cells requires several key events including phagocytosis, phagolysosomal maturation impairment, and parasite replication. Autophagy is accountable for the physiological turnover of cellular organelles, degradation of macromolecular structures, and pathogen elimination. Read More

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Copy number-dependent DNA methylation of the Pyricularia oryzae MAGGY retrotransposon is triggered by DNA damage.

Commun Biol 2021 Mar 19;4(1):351. Epub 2021 Mar 19.

Laboratory of Cell Function and Structure, Graduate School of Agricultural Science, Kobe University, Nada Kobe, Japan.

Transposable elements are common targets for transcriptional and post-transcriptional gene silencing in eukaryotic genomes. However, the molecular mechanisms responsible for sensing such repeated sequences in the genome remain largely unknown. Here, we show that machinery of homologous recombination (HR) and RNA silencing play cooperative roles in copy number-dependent de novo DNA methylation of the retrotransposon MAGGY in the fungus Pyricularia oryzae. Read More

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Host sunflower-induced silencing of parasitism-related genes confers resistance to invading Orobanche cumana.

Plant Physiol 2021 Mar;185(2):424-440

Key Laboratory of Forage and Endemic Crop Biotechnology, Ministry of Education, School of Life Sciences, Inner Mongolia University, Hohhot 010070, P. R. China.

Orobanche cumana is a holoparasitic plant that attaches to host-plant roots and seriously reduces the yield of sunflower (Helianthus annuus L.). Effective control methods are lacking with only a few known sources of genetic resistance. Read More

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The Heat Shock Protein 40-Type Chaperone MASH Supports the Endoplasmic Reticulum-Associated Degradation E3 Ubiquitin Ligase MAKIBISHI1 in .

Front Plant Sci 2021 23;12:639625. Epub 2021 Feb 23.

Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.

Jasmonates (JA) are oxylipin-derived phytohormones that trigger the production of specialized metabolites that often serve in defense against biotic stresses. In , a JA-induced endoplasmic reticulum-associated degradation (ERAD)-type machinery manages the production of bioactive triterpenes and thereby secures correct plant metabolism, growth, and development. This machinery involves the conserved RING membrane-anchor (RMA)-type E3 ubiquitin ligase MAKIBISHI1 (MKB1). Read More

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February 2021

Dri1 mediates heterochromatin assembly via RNAi and histone deacetylation.

Genetics 2021 Mar 8. Epub 2021 Mar 8.

Department of Biology, New York University, 1009 Silver Center, 100 Washington Square East, New York, NY, USA.

Heterochromatin, a transcriptionally silenced chromatin domain, is important for genome stability and gene expression. Histone 3 lysine 9 methylation (H3K9me) and histone hypoacetylation are conserved epigenetic hallmarks of heterochromatin. In fission yeast, RNA interference (RNAi) plays a key role in H3K9 methylation and heterochromatin silencing. Read More

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Establishment of Novel Protein Interaction Assays between Sin3 and REST Using Surface Plasmon Resonance and Time-Resolved Fluorescence Energy Transfer.

Int J Mol Sci 2021 Feb 26;22(5). Epub 2021 Feb 26.

Center for Therapeutic Innovation, Gene Research Center for Frontiers Life Sciences, Nagasaki University, Graduate School of Biomedical Sciences, 1-12-14 Sakamoto, Nagasaki 852-8523, Japan.

Repressor element-1 (RE-1) or neural restrictive silencer element (NRSE) bound with a zinc finger transcription repressor, RE-1 silencing transcription factor (REST, also known as neural restrictive silencer factor, NRSF) has been identified as a fundamental repressor element in many genes, including neuronal genes. Genes regulated by REST/NRSF regulate multifaceted neuronal phenotypes, and their defects in the machinery cause neuropathies, disorders of neuron activity), autism and so on. In REST repressions, the N-terminal repressor domain recruits Sin3B via its paired amphipathic helix 1 (PAH1) domain, which plays an important role as a scaffold for histone deacetylase 1 and 2. Read More

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February 2021

Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR-874-3P/ATG16L1 axis.

Mol Oncol 2021 Apr 27;15(4):1203-1216. Epub 2021 Feb 27.

Department of Pediatric Hematology, Affiliated Hospital of Jining Medical University, China.

Autophagy is an important mechanism involved in the regulation of acute myeloid leukemia (AML) chemoresistance. The long noncoding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (DANCR) exhibits oncogenic activity in several types of human cancers, including AML, but it remains unclear whether it regulates autophagy and chemoresistance in AML. We report here that cytarabine (Ara-C) treatment elevates DANCR expression in human AML cells. Read More

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Insufficient Radiofrequency Ablation Promotes Hepatocellular Carcinoma Metastasis through m A mRNA Methylation Dependent Mechanism.

Hepatology 2021 Feb 26. Epub 2021 Feb 26.

Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

The dynamic N6-methyladenosine (m A) mRNA modification is essential for acute stress response and cancer progression. Sublethal heat stress from insufficient radiofrequency ablation (IRFA) has been confirmed to promote hepatocellular carcinoma (HCC) progression, however, whether m A machinery is involved in IRFA-induced HCC recurrence remains unknown. Using IRFA HCC orthotopic mouse model, we detected higher level of m A reader YTHDF1 in the sublethal-heat-exposed transitional zone close to the ablation center than that in the farther area. Read More

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February 2021

Metformin alleviates cisplatin-induced ototoxicity by autophagy induction possibly via the AMPK/FOXO3a pathway.

J Neurophysiol 2021 04 24;125(4):1202-1212. Epub 2021 Feb 24.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

Cisplatin is an antitumor drug that is widely used for the treatment of various solid tumors. Unfortunately, patients are often troubled by serious side effects, especially hearing loss. Up to now, there have been no clear and effective measures to prevent cisplatin-induced ototoxicity in clinical use. Read More

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microRNA-induced translational control of antiviral immunity by the cap-binding protein 4EHP.

Mol Cell 2021 03 12;81(6):1187-1199.e5. Epub 2021 Feb 12.

Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada. Electronic address:

Type I interferons (IFNs) are critical cytokines in the host defense against invading pathogens. Sustained production of IFNs, however, is detrimental to the host, as it provokes autoimmune diseases. Thus, the expression of IFNs is tightly controlled. Read More

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The ubiquitin isopeptidase USP10 deubiquitinates LC3B to increase LC3B levels and autophagic activity.

J Biol Chem 2021 Feb 9:100405. Epub 2021 Feb 9.

Neurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, 20892, USA.

Components of the autophagy machinery are subject to regulation by various post-translational modifications. Previous studies have shown that monoubiquitination of LC3B catalyzed by the ubiquitin-activating enzyme UBA6 and ubiquitin-conjugating enzyme/ubiquitin ligase BIRC6 targets LC3B for proteasomal degradation, thus reducing LC3B levels and autophagic activity under conditions of stress. However, mechanisms capable of counteracting this process are not known. Read More

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February 2021

Extensive Analysis of miRNA Trimming and Tailing Indicates that AGO1 Has a Complex Role in miRNA Turnover.

Plants (Basel) 2021 Jan 30;10(2). Epub 2021 Jan 30.

Instituto de Agrobiotecnología del Litoral (CONICET-UNL), Cátedra de Biología Celular y Molecular, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, 3000 Santa Fe, Argentina.

MicroRNAs are small regulatory RNAs involved in several processes in plants ranging from development and stress responses to defense against pathogens. In order to accomplish their molecular functions, miRNAs are methylated and loaded into one ARGONAUTE (AGO) protein, commonly known as AGO1, to stabilize and protect the molecule and to assemble a functional RNA-induced silencing complex (RISC). A specific machinery controls miRNA turnover to ensure the silencing release of targeted-genes in given circumstances. Read More

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January 2021

AAV-Mediated CRISPRi and RNAi Based Gene Silencing in Mouse Hippocampal Neurons.

Cells 2021 Feb 4;10(2). Epub 2021 Feb 4.

Forschungszentrum Jülich, Institute of Biological Information Processing, IBI-1, Leo-Brandt-Straße, 52428 Jülich, Germany.

Uncovering the physiological role of individual proteins that are part of the intricate process of cellular signaling is often a complex and challenging task. A straightforward strategy of studying a protein's function is by manipulating the expression rate of its gene. In recent years, the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9-based technology was established as a powerful gene-editing tool for generating sequence specific changes in proliferating cells. Read More

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February 2021

Influence of the disordered domain structure of MeCP2 on its structural stability and dsDNA interaction.

Int J Biol Macromol 2021 Apr 3;175:58-66. Epub 2021 Feb 3.

Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI, and GBsC-CSIC-BIFI, Universidad de Zaragoza, Zaragoza 50018, Spain; Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, 50009 Zaragoza, Spain; Fundación ARAID, Gobierno de Aragón, 50018 Zaragoza, Spain. Electronic address:

Methyl-CpG binding protein 2 (MeCP2) is a transcriptional regulator and a chromatin-associated structural protein. MeCP2 deregulation results in two neurodevelopmental disorders: MeCP2 dysfunction is associated with Rett syndrome, while excess of activity is associated with MeCP2 duplication syndrome. MeCP2 is an intrinsically disordered protein (IDP) constituted by six structural domains with variable, small percentage of well-defined secondary structure. Read More

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Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in .

Elife 2021 Feb 4;10. Epub 2021 Feb 4.

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.

In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the anoramix-nduced o-ranscriptional ilencing (PICTS) complex, containing Panoramix, Nxf2 and Nxt1. Here, we report that the highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component of the PICTS complex. Read More

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February 2021