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MicroRNA profiling of Neospora caninum tachyzoites (NC-1) using a high-throughput approach.

Parasitol Res 2021 Apr 24. Epub 2021 Apr 24.

Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun, 130062, China.

Neospora caninum is an important pathogen commonly causing spontaneous abortion in livestock. The parasite is known to remain in cysts in an inactive state; or it can undergo expansive development within an intermediate host. However, the mechanisms that trigger the proliferation of N. Read More

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A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage.

Elife 2021 04 13;10. Epub 2021 Apr 13.

Calico Life Sciences LLC, South San Francisco, United States.

Somatic cells age and die, but the germ-cell lineage is immortal. In , germline immortality involves proteostasis renewal at the beginning of each new generation, when oocyte maturation signals from sperm trigger the clearance of carbonylated proteins and protein aggregates. Here, we explore the cell biology of this proteostasis renewal in the context of a whole-genome RNAi screen. Read More

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Sex peptide receptor mediates the post-mating switch in Helicoverpa armigera (Lepidoptera: Noctuidae) female reproductive behavior.

Pest Manag Sci 2021 Apr 2. Epub 2021 Apr 2.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.

Background: In Drosophila, the sex peptide receptor (SPR) in females to detect male sex peptide (SP) and trigger changes in female behavior including mating rejection and oviposition. In moths, the SPR had been identified and investigated the limited function by using RNA interference (RNAi). However, the detailed function of SPR after a normal mating in moths, especially the role in female sexual receptivity, remains to be elucidated. Read More

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Complex -Glycans Are Important for Normal Fruit Ripening and Seed Development in Tomato.

Front Plant Sci 2021 9;12:635962. Epub 2021 Mar 9.

Institute of Plant Biology and Biotechnology, University of Münster, Münster, Germany.

Complex -glycan modification of secretory glycoproteins in plants is still not well understood. Essential in animals, where a lack of complex -glycans is embryo-lethal, their presence in plants seemed less relevant for a long time mostly because mutants lacking -acetyl-glucosaminyltransferase I (GNTI, the enzyme initiating complex -glycan maturation in the Golgi apparatus) are viable and showed only minor impairments regarding stress tolerance or development. A different picture emerged when a rice () T-DNA mutant was found to be unable to reach the reproductive stage. Read More

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Secondary siRNAs in Plants: Biosynthesis, Various Functions, and Applications in Virology.

Front Plant Sci 2021 2;12:610283. Epub 2021 Mar 2.

Advanced Center for Plant Virology, Division of Plant Pathology, Indian Agricultural Research Institute, New Delhi, India.

The major components of RNA silencing include both transitive and systemic small RNAs, which are technically called secondary sRNAs. Double-stranded RNAs trigger systemic silencing pathways to negatively regulate gene expression. The secondary siRNAs generated as a result of transitive silencing also play a substantial role in gene silencing especially in antiviral defense. Read More

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VDAC1 promotes cardiomyocyte autophagy in anoxia/reoxygenation injury via the PINK1/Parkin pathway.

Cell Biol Int 2021 Mar 6. Epub 2021 Mar 6.

Jiangxi Provincial Key Laboratory of Basic Pharmacology, Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, China.

Ischemia/reperfusion (I/R) is a well-known injury to the myocardium, but the mechanism involved remains elusive. In addition to the well-accepted apoptosis theory, autophagy was recently found to be involved in the process, exerting a dual role as protection in ischemia and detriment in reperfusion. Activation of autophagy is mediated by mitochondrial permeability transition pore (MPTP) opening during reperfusion. Read More

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The Risks of miRNA Therapeutics: In a Drug Target Perspective.

Drug Des Devel Ther 2021 22;15:721-733. Epub 2021 Feb 22.

Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China.

RNAi therapeutics have been growing. Patisiran and givosiran, two siRNA-based drugs, were approved by the Food and Drug Administration in 2018 and 2019, respectively. However, there is rare news on the advance of miRNA drugs (another therapeutic similar to siRNA drug). Read More

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February 2021

Ribosome stalling and SGS3 phase separation prime the epigenetic silencing of transposons.

Nat Plants 2021 03 1;7(3):303-309. Epub 2021 Mar 1.

National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences (CEMPS), Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

Transposable elements (TEs, transposons) are mobile DNAs that can cause fatal mutations. To suppress their activity, host genomes deploy small interfering RNAs (siRNAs) that trigger and maintain their epigenetic silencing. Whereas 24-nucleotide (nt) siRNAs mediate RNA-directed DNA methylation (RdDM) to reinforce the silent state of TEs, activated or naive TEs give rise to 21- or 22-nt siRNAs by the RNA-DEPENDENT RNA POLYMERASE 6 (RDR6)-mediated pathway, triggering both RNAi and de novo DNA methylation. Read More

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Emerging role of RNA interference in immune cells engineering and its therapeutic synergism in immunotherapy.

Br J Pharmacol 2021 Apr 17;178(8):1741-1755. Epub 2021 Mar 17.

Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.

RNAi effectors (e.g. siRNA, shRNA and miRNA) can trigger the silencing of specific genes causing alteration of genomic functions becoming a new therapeutic area for the treatment of infectious diseases, neurodegenerative disorders and cancer. Read More

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Effect of Grafting on Viral Resistance of Non-transgenic Plum Scion Combined With Transgenic PPV-Resistant Rootstock.

Front Plant Sci 2021 1;12:621954. Epub 2021 Feb 1.

Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Pushchino, Russia.

In stone fruit trees, resistance to (PPV) can be achieved through the specific degradation of viral RNA by the mechanism of RNA interference (RNAi). Transgenic virus-resistant plants, however, raise serious biosafety concerns due to the insertion and expression of hairpin constructs that usually contain various selective foreign genes. Since a mature stone tree represents a combination of scion and rootstock, grafting commercial varieties onto transgenic virus-tolerant rootstocks is a possible approach to mitigate biosafety problems. Read More

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February 2021

Lentiviral transduction facilitates RNA interference in the nematode parasite Nippostrongylus brasiliensis.

PLoS Pathog 2021 01 26;17(1):e1009286. Epub 2021 Jan 26.

Department of Life Sciences, Imperial College London, London, United Kingdom.

Animal-parasitic nematodes have thus far been largely refractory to genetic manipulation, and methods employed to effect RNA interference (RNAi) have been ineffective or inconsistent in most cases. We describe here a new approach for genetic manipulation of Nippostrongylus brasiliensis, a widely used laboratory model of gastrointestinal nematode infection. N. Read More

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January 2021

ATR Kinase Is a Crucial Player Mediating the DNA Damage Response in .

Front Cell Dev Biol 2020 22;8:602956. Epub 2020 Dec 22.

Laboratory of Cell Cycle (LCC), Center of Toxins, Immune Response and Cell Signaling (CETICs), Butantan Institute, São Paulo, Brazil.

DNA double-strand breaks (DSBs) are among the most deleterious lesions that threaten genome integrity. To address DSBs, eukaryotic cells of model organisms have evolved a complex network of cellular pathways that are able to detect DNA damage, activate a checkpoint response to delay cell cycle progression, recruit the proper repair machinery, and resume the cell cycle once the DNA damage is repaired. Cell cycle checkpoints are primarily regulated by the apical kinases ATR and ATM, which are conserved throughout the eukaryotic kingdom. Read More

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December 2020

Targeting alternative splicing by RNAi: from the differential impact on splice variants to triggering artificial pre-mRNA splicing.

Nucleic Acids Res 2021 01;49(2):1133-1151

Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences Vienna, Vienna 1190, Austria.

Alternative splicing generates multiple transcript and protein isoforms from a single gene and controls transcript intracellular localization and stability by coupling to mRNA export and nonsense-mediated mRNA decay (NMD). RNA interference (RNAi) is a potent mechanism to modulate gene expression. However, its interactions with alternative splicing are poorly understood. Read More

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January 2021

Off-target effects of RNAi correlate with the mismatch rate between dsRNA and non-target mRNA.

RNA Biol 2021 Jan 4:1-13. Epub 2021 Jan 4.

The Key Laboratory of Monitoring and Management of Plant Diseases and Insects/Department of Entomology, College of Plant Protection, Nanjing Agricultural University , Nanjing, China.

RNAi is a potent technique for the knockdown of target genes. However, its potential off-target effects limit the widespread applications in both reverse genetic analysis and genetic manipulation. Previous efforts have uncovered rules underlying specificity of siRNA-based silencing, which has broad applications in humans, but the basis for specificity of dsRNAs, which are better suited for use as insecticides, is poorly understood. Read More

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January 2021

α- and β-Santalols Delay Aging in via Preventing Oxidative Stress and Protein Aggregation.

ACS Omega 2020 Dec 10;5(50):32641-32654. Epub 2020 Dec 10.

Department of Zoology, Bharathiar University, Coimbatore, Tamilnadu 641046, India.

α- and β-Santalol (santalol isomers) are the most abundant sesquiterpenoids found in sandalwood, contributing to its pleasant fragrance and wide-spectrum bioactivity. This study aimed at identifying the antiaging and antiaggregation mechanism of α- and β-santalol using the genetic tractability of an model . The results showed that santalol isomers retard aging, improved health span, and inhibited the aggregation of toxic amyloid-β (Aβ) and polyglutamine repeats (Q35, Q40, and HtnQ150) in models for Alzheimer's and Huntington's disease, respectively. Read More

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December 2020

Activity-dependent endocytosis of Wingless regulates synaptic plasticity in the Drosophila visual system.

Genes Genet Syst 2021 Feb 6;95(5):235-247. Epub 2021 Feb 6.

Graduate School of Life Science and Technology, Tokyo Institute of Technology.

Neural activity contributes to synaptic regulation in sensory systems, which allows organisms to adjust to changing environments. However, little is known about how synaptic molecular components are regulated to achieve activity-dependent plasticity at central synapses. Previous studies have shown that following prolonged exposure to natural ambient light, the presynaptic active zone (AZ), an area associated with presynaptic neurotransmitter release in Drosophila photoreceptors, undergoes reversible remodeling. Read More

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February 2021

Identification of oligo-adenylated small RNAs in the parasite Entamoeba and a potential role for small RNA control.

BMC Genomics 2020 Dec 9;21(1):879. Epub 2020 Dec 9.

Division of Infectious Diseases, Department of Internal Medicine, Stanford University School of Medicine, S-143 Grant Building, 300 Pasteur Drive, Stanford, CA, 94305-5107, USA.

Background: The RNA interference (RNAi) pathway is a gene regulation mechanism that utilizes small RNA (sRNA) and Argonaute (Ago) proteins to silence target genes. Our previous work identified a functional RNAi pathway in the protozoan parasite Entamoeba histolytica, including abundant 27 nt antisense sRNA populations which associate with EhAgo2-2 protein. However, there is lack of understanding about the sRNAs that are bound to two other EhAgos (EhAgo2-1 and 2-3), and the mechanism of sRNA regulation itself is unclear in this parasite. Read More

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December 2020

Cathepsin B is a mediator of organelle-specific initiation of ferroptosis.

Biochem Biophys Res Commun 2020 12 22;533(4):1464-1469. Epub 2020 Oct 22.

The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510510, China; Department of Surgery, UT Southwestern Medical Center, Dallas, TX, 75390, USA. Electronic address:

Ferroptosis is a type of non-apoptotic regulated cell death that involves excessive iron accumulation and subsequent lipid peroxidation. Although the antioxidant mechanisms of ferroptosis have been extensively studied recently, little is known about the interactions between the different organelles that control ferroptosis. Here, we show that the translocation of lysosomal cysteine protease cathepsin B (CTSB) into the nucleus is an important molecular event that mediates organelle-specific initiation of ferroptosis in human pancreatic cancer cells. Read More

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December 2020

TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation.

Int J Mol Sci 2020 Nov 23;21(22). Epub 2020 Nov 23.

Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Vavilova str. 26, 119991 Moscow, Russia.

Robertsonian (centric-fusion) translocation is the form of chromosomal translocation in which two long arms of acrocentric chromosomes are fused to form one metacentric. These translocations reduce the number of chromosomes while preserving existing genes and are considered to contribute to speciation. We asked whether hypomorphic mutations in genes that disrupt the formation of pericentromeric regions could lead to centric fusion. Read More

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November 2020

Insecticidal RNA interference, thinking beyond long dsRNA.

Authors:
Alex S Flynt

Pest Manag Sci 2021 May 4;77(5):2179-2187. Epub 2020 Nov 4.

Cellular and Molecular Biology, University of Southern Mississippi, Hattiesburg, MS, USA.

Over 20 years ago double-stranded RNA (dsRNA) was described as the trigger of RNAi interference (RNAi)-based gene silencing. This paradigm has held since, especially for insect biopesticide technologies where dsRNAs, similar to those described in 1998, are used to inhibit gene expression. In the intervening years, investigation of RNAi pathways has revealed the small RNA effectors of RNAi are diverse and rapidly evolving. Read More

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Motif 1 Binding Protein suppresses wingless to promote eye fate in Drosophila.

Sci Rep 2020 10 14;10(1):17221. Epub 2020 Oct 14.

Department of Biology, University of Dayton, Dayton, OH, 45469, USA.

The phenomenon of RNA polymerase II (Pol II) pausing at transcription start site (TSS) is one of the key rate-limiting steps in regulating genome-wide gene expression. In Drosophila embryo, Pol II pausing is known to regulate the developmental control genes expression, however, the functional implication of Pol II pausing during later developmental time windows remains largely unknown. A highly conserved zinc finger transcription factor, Motif 1 Binding Protein (M1BP), is known to orchestrate promoter-proximal pausing. Read More

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October 2020

Iron deficiency and the loss of chloroplast iron-sulfur cluster assembly trigger distinct transcriptome changes in Arabidopsis rosettes.

Metallomics 2020 11 13;12(11):1748-1764. Epub 2020 Oct 13.

Biology Department, Colorado State University, 2515 W. Pitkin Street, Fort Collins, CO 80523-1878, USA.

Regulation of mRNA abundance revealed a genetic program for plant leaf acclimation to iron (Fe) limitation. The transcript for SUFB, a key component of the plastid iron-sulfur (Fe-S) assembly pathway is down-regulated early after Fe deficiency, and prior to down-regulation of mRNAs encoding abundant chloroplast Fe containing proteins, which should economize the use of Fe. What controls this system is unclear. Read More

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November 2020

Chilling Stress Triggers VvAgo1-Mediated miRNA-Like RNA Biogenesis in .

Front Microbiol 2020 15;11:523593. Epub 2020 Sep 15.

Key Laboratory of Edible Fungi Resources and Utilization (South), National Engineering Research Center of Edible Fungi, Ministry of Agriculture, Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, Shanghai, China.

In , an important species of edible mushroom, cryogenic autolysis is a typical phenomenon that occurs during abnormal metabolism. Analysis of gene expression profiling and qPCR showed that chilling stress (CS) significantly and continuously upregulated only one type of Argonaute in , i.e. Read More

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September 2020

Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside.

Pharmaceuticals (Basel) 2020 Oct 7;13(10). Epub 2020 Oct 7.

Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, USA.

The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. Read More

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October 2020

An ATP synthase beta subunit is required for internalization of dsRNA into shrimp cells.

Fish Shellfish Immunol 2020 Nov 10;106:948-958. Epub 2020 Sep 10.

Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakhon Pathom, 73170, Thailand. Electronic address:

Extracellular double-stranded RNA (dsRNA) is an important modulator in innate immunity in both vertebrates and invertebrates. In shrimp, extracellular dsRNA can trigger RNAi pathway and serves as antiviral defense mechanism. However, the mechanism of dsRNA internalization into the cells has not yet known in shrimp cells. Read More

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November 2020

Three Rules Explain Transgenerational Small RNA Inheritance in C. elegans.

Cell 2020 09 24;182(5):1186-1197.e12. Epub 2020 Aug 24.

Department of Neurobiology, Wise Faculty of Life Sciences & Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address:

Experiences trigger transgenerational small RNA-based responses in C. elegans nematodes. Dedicated machinery ensures that heritable effects are reset, but how the responses segregate in the population is unknown. Read More

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September 2020

Loss of G protein pathway suppressor 2 in human adipocytes triggers lipid remodeling by upregulating ATP binding cassette subfamily G member 1.

Mol Metab 2020 12 13;42:101066. Epub 2020 Aug 13.

Department of Biosciences and Nutrition, Karolinska Institute, 14183 Huddinge, Sweden. Electronic address:

Objective: Adipogenesis is critical for adipose tissue remodeling during the development of obesity. While the role of transcription factors in the orchestration of adipogenic pathways is already established, the involvement of coregulators that transduce regulatory signals into epigenome alterations and transcriptional responses remains poorly understood. The aim of our study was to investigate which pathways are controlled by G protein pathway suppressor 2 (GPS2) during the differentiation of human adipocytes. Read More

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December 2020

Small RNA Extraction and Quantification of Isolated Fungal Cells from Plant Tissue by the Sequential Protoplastation.

Methods Mol Biol 2021 ;2170:219-229

Department of Plant Pathology and Microbiology, Center for Plant Cell Biology and Institute for Integrative Genome Biology, University of California, Riverside, CA, USA.

Small RNA (sRNA)-mediated RNA interference (RNAi) is critical for regulating both host immunity and pathogen virulence. Recent studies have revealed that RNA-silencing signals travel between different organisms and trigger gene silencing in trans, termed cross-kingdom RNAi. To investigate cross-kingdom RNAi, it is necessary to purify the fungal cells of interest from infected plants. Read More

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Exploiting somatic piRNAs in i enables novel gene silencing through RNA feeding.

Life Sci Alliance 2020 10 6;3(10). Epub 2020 Aug 6.

Cellular and Molecular Biology, University of Southern Mississippi, Hattiesburg, MS, USA

RNAi promises to reshape pest control by being nontoxic, biodegradable, and species specific. However, due to the plastic nature of RNAi, there is a significant variability in responses. In this study, we investigate small RNA pathways and processing of ingested RNAi trigger molecules in a hemipteran plant pest, the whitefly Unlike , where the paradigm for insect RNAi technology was established, whitefly has abundant somatic piwi-associated RNAs (piRNAs). Read More

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October 2020

Mechanism and Function of Antiviral RNA Interference in Mice.

mBio 2020 08 4;11(4). Epub 2020 Aug 4.

Department of Microbiology and Plant Pathology, University of California, Riverside, Riverside, California, USA

Distinct mammalian RNA viruses trigger Dicer-mediated production of virus-derived small-interfering RNAs (vsiRNA) and encode unrelated proteins to suppress vsiRNA biogenesis. However, the mechanism and function of the mammalian RNA interference (RNAi) response are poorly understood. Here, we characterized antiviral RNAi in a mouse model of infection with Nodamura virus (NoV), a mosquito-transmissible positive-strand RNA virus encoding a known double-stranded RNA (dsRNA)-binding viral suppressor of RNAi (VSR), the B2 protein. Read More

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