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Rna degradation

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https://www.readbyqxmd.com/read/29792692/small-molecule-targeted-recruitment-of-a-nuclease-to-rna
#1
Matthew G Costales, Yasumasa Matsumoto, Sai Pradeep Velagapudi, Matthew D Disney
The choreography between RNA synthesis and degradation is a key determinant in biology. Engineered systems such as CRISPR have been developed to rid a cell of RNAs. Here, we show that a small molecule can recruit a nuclease to a specific transcript, triggering its destruction. A small molecule that selectively binds the oncogenic microRNA(miR)-96 hairpin precursor was appended with a short 2'-5' poly(A) oligonucleotide. The conjugate locally activated endogenous, latent ribonuclease (RNase L), which selectively cleaved the miR-96 precursor in cancer cells in a catalytic and sub-stoichiometric fashion...
May 24, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29790953/identifying-and-avoiding-off-target-effects-of-rnase-h-dependent-antisense-oligonucleotides-in-mice
#2
Peter H Hagedorn, Malene Pontoppidan, Tina S Bisgaard, Marco Berrera, Andreas Dieckmann, Martin Ebeling, Marianne R Møller, Heidi Hudlebusch, Marianne L Jensen, Henrik F Hansen, Troels Koch, Morten Lindow
Antisense oligonucleotides that are dependent on RNase H for cleavage and subsequent degradation of complementary RNA are being developed as therapeutics. Besides the intended RNA target, such oligonucleotides may also cause degradation of unintended RNA off-targets by binding to partially complementary target sites. Here, we characterized the global effects on the mouse liver transcriptome of four oligonucleotides designed as gapmers, two targeting Apob and two targeting Pcsk9, all in different regions on their respective intended targets...
May 22, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29790300/aspiration-pneumonia-induces-muscle-atrophy-in-the-respiratory-skeletal-and-swallowing-systems
#3
Riyo Komatsu, Tatsuma Okazaki, Satoru Ebihara, Makoto Kobayashi, Yoko Tsukita, Mayumi Nihei, Hisatoshi Sugiura, Kaijun Niu, Takae Ebihara, Masakazu Ichinose
BACKGROUND: Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle...
May 22, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29789676/the-angiotensin-i-converting-enzyme-insertion-deletion-in-polymorphic-element-codes-for-an-aluya5-rna-that-downregulates-gene-expression
#4
REVIEW
Fernando F P Mafra, Pedro P Gattai, Michel M Macedo, Marcelo A Mori, Ronaldo C Araujo
Angiotensin-I-converting enzyme (ACE) is involved in the synthesis and degradation of important bioactive peptides. The ACE gene has a 287-bp insertion/deletion polymorphism that controls ACE expression through a mechanism that remains elusive. In this study, we found that the 287-bp polymorphic element of the ACE gene, a member of the AluYa5 sub-family of Alu elements, codes for an RNA molecule that controls the levels of ACE mRNA. Transient transfection of a plasmid containing a CMV promoter upstream of the ACE polymorphic element resulted in significant expression of an AluYa5 RNA and reduced ACE mRNA expression as well as ACE enzymatic activity in AD 293 cells...
May 23, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29788394/rna-interference-of-the-muscle-actin-gene-in-bed-bugs-exploring-injection-versus-topical-application-for-dsrna-delivery
#5
Sanjay Basnet, Shripat T Kamble
Bed bugs are one the most troublesome household pests that feed primarily on human blood. RNA interference (RNAi) is currently being pursued as a potential tool for insect population management and has shown efficacy against some phytophagous insects. We evaluated the different techniques to deliver dsRNA specific to bed bug muscle actin (dsactin) into bed bugs. Initially, stability of dsRNA in human blood was studied to evaluate the feasibility of feeding method. Adult bed bugs were injected with dsRNA between last thoracic segment and first abdominal segment on the ventral side, with a dose of 0...
May 1, 2018: Journal of Insect Science
https://www.readbyqxmd.com/read/29786968/p62-mediated-autophagy-affects-nutrition-dependent-insulin-receptor-substrate-1-dynamics-in-3t3-l1-preadipocytes
#6
Hirobumi Igawa, Akihiro Kikuchi, Hirofumi Misu, Kiyo-Aki Ishii, Shuichi Kaneko, Toshinari Takamura
AIMS/INTRODUCTION: Previous studies have shown that the organism's nutritional status changes the protein levels of insulin receptor substrate 1 (IRS-1) in a tissue-specific manner. Although the mechanisms underlying the regulation of IRS-1 in the nutrient-rich conditions associated with diabetes and insulin resistance have been well studied, those under nutrient-poor conditions remain unknown. The aim of this study was to investigate how IRS-1 protein levels change depending on the nutritional status of 3T3-L1 preadipocytes...
May 22, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29784949/neuronal-activity-regulates-drosha-via-autophagy-in-spinal-muscular-atrophy
#7
Inês do Carmo G Gonçalves, Johanna Brecht, Maximilian P Thelen, Wiebke A Rehorst, Miriam Peters, Hyun Ju Lee, Susanne Motameny, Laura Torres-Benito, Darius Ebrahimi-Fakhari, Natalia L Kononenko, Janine Altmüller, David Vilchez, Mustafa Sahin, Brunhilde Wirth, Min Jeong Kye
Dysregulated miRNA expression and mutation of genes involved in miRNA biogenesis have been reported in motor neuron diseases including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Therefore, identifying molecular mechanisms governing miRNA expression is important to understand these diseases. Here, we report that expression of DROSHA, which is a critical enzyme in the microprocessor complex and essential for miRNA biogenesis, is reduced in motor neurons from an SMA mouse model. We show that DROSHA is degraded by neuronal activity induced autophagy machinery, which is also dysregulated in SMA...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29782974/molecular-therapy-using-sirna-recent-trends-and-advances-of-multi-target-inhibition-of-cancer-growth
#8
REVIEW
Shweta Jain, Kamla Pathak, Ankur Vaidya
RNA interference (RNAi) therapy, harnessed to produce a new class of drugs for treatment, has drawn attention and seen steady progress over the years. Molecular therapy using biological macromolecules small interfering RNA (siRNA) for gene silencing has received significant attention to target cancer-related genes. Basically, siRNA molecules bind to messenger RNAs (mRNA) by complementary base pairing, to induce degradation of the mRNA and/or block protein synthesis. Numerous genes and gene related proteins have been reported till date to target in siRNA based cancer therapy...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782532/hepatitis-c-virus-ns4b-induces-the-degradation-of-trif-to-inhibit-tlr3-mediated-interferon-signaling-pathway
#9
Yisha Liang, Xuezhi Cao, Qiang Ding, Yanan Zhao, Zhenliang He, Jin Zhong
Toll-like receptor 3 (TLR3) senses dsRNA intermediates produced during RNA virus replication to activate innate immune signaling pathways through adaptor protein TRIF. Many viruses have evolved strategies to block TLR3-mediated interferon signaling via targeting TRIF. Here we studied how hepatitis C virus (HCV) antagonizes the TLR3-mediated interferon signaling. We found that HCV-encoded NS4B protein inhibited TLR3-mediated interferon signaling by down-regulating TRIF protein level. Mechanism studies indicated that the downregulation of TRIF by NS4B was dependent on caspase8...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782024/investigation-of-rna-synthesis-using-5-bromouridine-labelling-and-immunoprecipitation
#10
Rikke H Kofoed, Cristine Betzer, Søren Lykke-Andersen, Ewa Molska, Poul H Jensen
When steady state RNA levels are compared between two conditions, it is not possible to distinguish whether changes are caused by alterations in production or degradation of RNA. This protocol describes a method for measurement of RNA production, using 5-Bromouridine labelling of RNA followed by immunoprecipitation, which enables investigation of RNA synthesized within a short timeframe (e.g., 1 h). The advantage of 5-Bromouridine-labelling and immunoprecipitation over the use of toxic transcriptional inhibitors, such as α-amanitin and actinomycin D, is that there are no or very low effects on cell viability during short-term use...
May 3, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29782023/double-stranded-rna-oral-delivery-methods-to-induce-rna-interference-in-phloem-and-plant-sap-feeding-hemipteran-insects
#11
Saikat Kumar B Ghosh, Wayne B Hunter, Alexis L Park, Dawn E Gundersen-Rindal
Phloem and plant sap feeding insects invade the integrity of crops and fruits to retrieve nutrients, in the process damaging food crops. Hemipteran insects account for a number of economically substantial pests of plants that cause damage to crops by feeding on phloem sap. The brown marmorated stink bug (BMSB), Halyomorpha halys (Heteroptera: Pentatomidae) and the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae) are hemipteran insect pests introduced in North America, where they are an invasive agricultural pest of high-value specialty, row, and staple crops and citrus fruits, as well as a nuisance pest when they aggregate indoors...
May 4, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29782022/practical-use-of-rna-interference-oral-delivery-of-double-stranded-rna-in-liposome-carriers-for-cockroaches
#12
Jia-Hsin Huang, Yun Liu, Yu-Hsien Lin, Xavier Belles, How-Jing Lee
RNA interference (RNAi) has been widely applied for uncovering the biological functions of numerous genes, and has been envisaged as a pest control tool operating by disruption of essential gene expression. Although different methods, such as injection, feeding, and soaking, have been reported for successful delivery of double-stranded RNA (dsRNA), the efficiency of RNAi through oral delivery of dsRNA is highly variable among different insect groups. The German cockroach, Blattella germanica, is highly sensitive to the injection of dsRNA, as shown by many studies published previously...
May 1, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781987/retrospective-microrna-sequencing-complementary-dna-library-preparation-protocol-using-formalin-fixed-paraffin-embedded-rna-specimens
#13
Olivier Loudig, Christina Liu, Thomas Rohan, Iddo Z Ben-Dov
-Archived, clinically classified formalin-fixed paraffin-embedded (FFPE) tissues can provide nucleic acids for retrospective molecular studies of cancer development. By using non-invasive or pre-malignant lesions from patients who later develop invasive disease, gene expression analyses may help identify early molecular alterations that predispose to cancer risk. It has been well described that nucleic acids recovered from FFPE tissues have undergone severe physical damage and chemical modifications, which make their analysis difficult and generally requires adapted assays...
May 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29777785/psmd2-regulates-breast-cancer-cell-proliferation-and-cell-cycle-progression-by-modulating-p21-and-p27-proteasomal-degradation
#14
Yunhai Li, Jing Huang, Beilei Zeng, Dejuan Yang, Jiazheng Sun, Xuedong Yin, Mengqi Lu, Zhu Qiu, Weiyan Peng, Tingxiu Xiang, Hongzhong Li, Guosheng Ren
Alterations in the ubiquitin-proteasome system (UPS) and UPS-associated proteins have been implicated in the development of many human malignancies. In this study, we investigated the expression profiles of 797 UPS-related genes using HiSeq data from The Cancer Genome Atlas and identified that PSMD2 was markedly upregulated in breast cancer. High PSMD2 expression was significantly correlated with poor prognosis. Gene set enrichment analysis revealed that transcriptome signatures involving proliferation, cell cycle, and apoptosis were critically enriched in specimens with elevated PSMD2...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29775646/the-rna-binding-protein-ars2-supports-hematopoiesis-at-multiple-levels
#15
Seerat Elahi, Shawn M Egan, G Aaron Holling, Rachel L Kandefer, Michael J Nemeth, Scott H Olejniczak
Recent biochemical characterization of Arsenic resistance protein 2 (Ars2) has established it as central to determining the fate of nascent RNA polymerase II (RNAPII) transcripts. Through interactions with the nuclear 5'-7-methylguanosine (7mG) cap binding complex (CBC), Ars2 promotes co-transcriptional processing coupled with nuclear export or degradation of several classes of RNAPII transcripts, allowing for gene expression programs that facilitate rapid and sustained proliferation of immortalized cells in culture...
May 15, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29774077/long-noncoding-rna-mir503hg-a-prognostic-indicator-inhibits-tumor-metastasis-by-regulating-the-hnrnpa2b1-nf-%C3%AE%C2%BAb-pathway-in-hepatocellular-carcinoma
#16
Hui Wang, Linhui Liang, Qiongzhu Dong, Lin Huan, Jia He, Botai Li, Chen Yang, Haojie Jin, Lin Wei, Chengtao Yu, Fangyu Zhao, Jinjun Li, Ming Yao, Wenxin Qin, Lunxiu Qin, Xianghuo He
Long noncoding RNAs (lncRNAs) have been associated with hepatocellular carcinoma (HCC), but the underlying molecular mechanisms of their specific association with hepatocarcinogenesis have not been fully explored. Methods: miR503HG was identified by microarray and validated by real-time PCR. Survival analysis was evaluated using the Kaplan-Meier method and assessed using the log-rank test. In vitro and in vivo assays were preformed to explore the biological effects of miR503HG in HCC cells. The interaction of miR503HG with HNRNPA2B1 was identified by RNA pull-down and RNA immunoprecipitation...
2018: Theranostics
https://www.readbyqxmd.com/read/29772800/identification-and-expression-of-mirnas-related-to-female-flower-induction-in-walnut-juglans-regia-l
#17
Li Zhou, Shaowen Quan, Hang Xu, Li Ma, Jianxin Niu
Flower induction is an essential stage in walnut ( Juglans regia L.) trees, directly affecting yield, yield stability, fruit quality and commodity value. The objective of this study was to identify miRNAs related to female flower induction via high-throughput sequencing and bioinformatics analysis. A total of 123 miRNAs were identified including 51 known miRNAs and 72 novel miRNAs. Differential expression was observed in 19 of the known miRNAs and 34 of the novel miRNAs. Twelve miRNAs were confirmed by RT-qPCR...
May 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29771965/evaluation-of-commercial-dna-and-rna-extraction-methods-for-high-throughput-sequencing-of-ffpe-samples
#18
Stine H Kresse, Heidi M Namløs, Susanne Lorenz, Jeanne-Marie Berner, Ola Myklebost, Bodil Bjerkehagen, Leonardo A Meza-Zepeda
Nucleic acid material of adequate quality is crucial for successful high-throughput sequencing (HTS) analysis. DNA and RNA isolated from archival FFPE material are frequently degraded and not readily amplifiable due to chemical damage introduced during fixation. To identify optimal nucleic acid extraction kits, DNA and RNA quantity, quality and performance in HTS applications were evaluated. DNA and RNA were isolated from five sarcoma archival FFPE blocks, using eight extraction protocols from seven kits from three different commercial vendors...
2018: PloS One
https://www.readbyqxmd.com/read/29771409/mir-299-5p-targets-cell-cycle-to-promote-cell-proliferation-and-progression-of-osteosarcoma
#19
C-L Zhang, L-B Li, C She, Y Xie, D-W Ge, Q-R Dong
OBJECTIVE: Osteosarcoma is a common primary bone tumor with high mortality. MicroRNA (miRNA, miR) is a small RNA with 20-25 nucleotides, which could regulate diverse biological processes by targeting 3'-UTR of gene to degrade it. MiR-299-5p has been reported to participate in the progression of many diseases, but the role in osteosarcoma is still uncertain. The aim of this work was to investigate the expression of miR-299-5p in osteosarcoma and its clinical significance. MATERIALS AND METHODS: The datasets of osteosarcoma miRNA was searched in Gene Expression Omnibus (GEO) datasets, including GSE65071, GSE39040, and GSE39055...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29769535/systematic-pan-cancer-analysis-of-somatic-allele-frequency
#20
Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A Crandall, Nathan Edwards, Anelia Horvath
Imbalanced expression of somatic alleles in cancer can suggest functional and selective features, and can therefore indicate possible driving potential of the underlying genetic variants. To explore the correlation between allele frequency of somatic variants and total gene expression of their harboring gene, we used the unique data set of matched tumor and normal RNA and DNA sequencing data of 5523 distinct single nucleotide variants in 381 individuals across 10 cancer types obtained from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Scientific Reports
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