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Rna induced silencing complex

Tong Sun, Shin-Yi Du, Joshua Armenia, Fangfang Qu, Jingyu Fan, Xiaodong Wang, Teng Fei, Kazumasa Komura, Shirley X Liu, Gwo-Shu Mary Lee, Philip W Kantoff
Mechanisms by which non-coding RNAs contribute to the progression of hormone-sensitive prostate cancer (PCa) (HSPC) to castration-resistant PCa (CRPC) remain largely unknown. We previously showed that microRNA-221/222 is up-regulated in CRPC and plays a critical role in modulating androgen receptor function during CRPC development. With further investigation, we characterized a putative promoter region located 23.3 kb upstream of the miR-221/222 gene, and this promoter is differentially activated in CRPC LNCaP-Abl cells, leading to the up-regulation of miR-221/222...
March 13, 2018: Oncogenesis
Bangari Haldipur, Prudhvi Lal Bhukya, Vidya Arankalle, Kavita Lole
Molecular mechanisms of liver pathology and clinical disease in HEV infection remain unclear. MicroRNAs are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection. In silico predictions using genotype 1, 2, 3 and 4 HEV sequences showed that majority of genomes (203/222) harbor at least one miR-122/miR-122* target site...
March 14, 2018: Journal of Virology
Daniel M Dayeh, Bradley C Kruithoff, Kotaro Nakanishi
Some gene transcripts have cellular functions as regulatory noncoding RNAs. For example, ~23 nucleotide (nt)-long small interfering RNAs (siRNAs) are loaded into Argonaute proteins. The resultant ribonucleoprotein assembly, the RNA-induced silencing complex (RISC), cleaves RNAs that are extensively base-paired with the loaded siRNA. To date, base complementarity is recognized as the major determinant of specific target cleavage (or slicing), but little is known about how Argonaute inspects base pairing before cleavage...
March 8, 2018: Journal of Biological Chemistry
Chang Li, Shouwen Du, Mingyao Tian, Yuhang Wang, Jieying Bai, Peng Tan, Wei Liu, Ronglan Yin, Maopeng Wang, Ying Jiang, Yi Li, Na Zhu, Yilong Zhu, Tiyuan Li, Shipin Wu, Ningyi Jin, Fuchu He
Interferons (IFNs) establish dynamic host defense mechanisms by inducing various IFN-stimulated genes that encodes many antiviral innate immune effectors. IFN-inducible transmembrane (IFITM) proteins have been identified as intrinsic antiviral effectors, which block the entry of a broad spectrum of enveloped RNA viruses by interrupting virus-endosomal fusion. However, antiviral activity of IFITM proteins against mammalian DNA virus has not been demonstrated till date. Here, we sought to investigate the antiviral activities and mechanisms of interferon-inducible transmembrane protein 3 (IFITM3) protein against poxvirus infection...
2018: Frontiers in Immunology
Shuyuan Shen, Hai Yu, Xiaobai Liu, Yunhui Liu, Jian Zheng, Ping Wang, Wei Gong, Jiajia Chen, Lini Zhao, Yixue Xue
The blood-tumor barrier (BTB) restricts the efficient delivery of anti-glioma drugs to cranial glioma tissues. Increased BTB permeability may allow greater delivery of the therapeutic agents. Increasing evidence has revealed that PIWI proteins and PIWI-interacting RNAs (piRNAs) play an important role in tumor progression. However, whether PIWI proteins and piRNAs regulate BTB permeability remains unclear. In the present study, we demonstrated that the PIWIL1/piRNA-DQ593109 (piR-DQ593109) complex was the predominant regulator of BTB permeability...
March 2, 2018: Molecular Therapy. Nucleic Acids
Qianru He, Lini Zhao, Yunhui Liu, Xiaobai Liu, Jian Zheng, Hai Yu, Heng Cai, Jun Ma, Libo Liu, Ping Wang, Zhen Li, Yixue Xue
Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which have been considered to mediate diverse tumorigenesis including angiogenesis. The present study aims to elucidate the potential role and molecular mechanism of circ-SHKBP1 in regulating the angiogenesis of U87 glioma-exposed endothelial cells (GECs). The expression of circ-SHKBP1, but not linear SHKBP1, was significantly upregulated in GECs compared with astrocyte-exposed endothelial cells (AECs). circ-SHKBP1 knockdown inhibited the viability, migration, and tube formation of GECs dramatically...
March 2, 2018: Molecular Therapy. Nucleic Acids
Xiaobai Liu, Jian Zheng, Yixue Xue, Chengbin Qu, Jiajia Chen, Zhenhua Wang, Zhen Li, Lei Zhang, Yunhui Liu
Long non-coding RNA (lncRNA) dysregulation is involved in tumorigenesis and regulation of diverse cellular processes in gliomas. lncRNA SNHG12 is upregulated and promotes cell growth in human osteosarcoma cells. TAR-DNA binding protein 43 (TDP43) functions as an oncogene in various tumors by modulating RNA expression. Downregulation of TDP43 or SNHG12 significantly inhibited malignant biological behaviors of glioma cells. miR-195, downregulated in glioma tissues and cells, significantly impaired the malignant progression of glioma cells...
March 2, 2018: Molecular Therapy. Nucleic Acids
Tao Zhang, Yen-Ching Wu, Patrick Mullane, Yon Ju Ji, Honghe Liu, Lu He, Amit Arora, Ho-Yon Hwang, Amelia F Alessi, Amirhossein G Niaki, Goran Periz, Lin Guo, Hejia Wang, Elad Elkayam, Leemor Joshua-Tor, Sua Myong, John K Kim, James Shorter, Shao-En Ong, Anthony K L Leung, Jiou Wang
MicroRNA-mediated gene silencing is a fundamental mechanism in the regulation of gene expression. It remains unclear how the efficiency of RNA silencing could be influenced by RNA-binding proteins associated with the microRNA-induced silencing complex (miRISC). Here we report that fused in sarcoma (FUS), an RNA-binding protein linked to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), interacts with the core miRISC component AGO2 and is required for optimal microRNA-mediated gene silencing...
March 1, 2018: Molecular Cell
Liangliang Zhang, Changmai Chen, Xinli Fan, Xinjing Tang
Caged siRNAs incorporating terminal modification were rationally designed for photochemical regulation of gene silencing induced by RNA interference (RNAi). Through the conjugation of a single oligonucleotide aptamer at the 5' terminus of the antisense RNA strand, enhancement of the blocking effect for RNA-induced silencing complex (RISC) formation/processing was expected, due both/either to the aptamers themselves and/or to their interaction with large binding proteins. Two oligonucleotide aptamers (AS1411 and MUC-1) were chosen for aptamer-siRNA conjugation through a photolabile linker...
February 28, 2018: Chembiochem: a European Journal of Chemical Biology
Miao Wang, Lyu Zhang, Zeyang Liu, Jiamin Zhou, Qi Pan, Jia Fan, Rongyu Zang, Lu Wang
AGO1 is a major component of RNA-induced silencing complexes and plays a crucial role in solid tumors. The aim of our study was to investigate AGO1 functions in hepatocellular carcinoma (HCC). Using small interfering RNA, AGO1 functions were investigated in HCCLM3 cell lines. Cell proliferation, immigration, and invasion significantly decreased after AGO1 depletion using MTT, wound-healing, and transwell assay. The associated proteins in the epithelial-mesenchymal transition (EMT) and the activation of its signal pathways were measured using western blot...
February 27, 2018: Cell Death & Disease
Anastasia V Balakireva, Andrey A Zamyatnin
Plant defense is achieved mainly through the induction of microbe-associated molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and RNA silencing. Plant immunity is a highly complex phenomenon with its own unique features that have emerged as a result of the arms race between plants and pathogens. However, the regulation of these processes is the same for all living organisms, including plants, and is controlled by proteases...
February 23, 2018: International Journal of Molecular Sciences
Hongyu Liu, Cheng Lei, Qin He, Zou Pan, Desheng Xiao, Yongguang Tao
MicroRNAs (miRNAs) are endogenous non-coding RNAs that contain approximately 22 nucleotides. They serve as key regulators in various biological processes and their dysregulation is implicated in many diseases including cancer and autoimmune disorders. It has been well established that the maturation of miRNAs occurs in the cytoplasm and miRNAs exert post-transcriptional gene silencing (PTGS) via RNA-induced silencing complex (RISC) pathway in the cytoplasm. However, numerous studies reaffirm the existence of mature miRNA in the nucleus, and nucleus-cytoplasm transport mechanism has also been illustrated...
February 22, 2018: Molecular Cancer
Gregoire Masliah, Christophe Maris, Sebastian Lb König, Maxim Yulikov, Florian Aeschimann, Anna L Malinowska, Julie Mabille, Jan Weiler, Andrea Holla, Juerg Hunziker, Nicole Meisner-Kober, Benjamin Schuler, Gunnar Jeschke, Frederic H-T Allain
The accurate cleavage of pre-micro(mi)RNAs by Dicer and mi/siRNA guide strand selection are important steps in forming the RNA-induced silencing complex (RISC). The role of Dicer binding partner TRBP in these processes remains poorly understood. Here, we solved the solution structure of the two N-terminal dsRNA binding domains (dsRBDs) of TRBP in complex with a functionally asymmetric siRNA using NMR, EPR, and single-molecule spectroscopy. We find that siRNA recognition by the dsRBDs is not sequence-specific but rather depends on the RNA shape...
February 15, 2018: EMBO Journal
Yan Lv, Yu Song, Chen Ni, Shaokai Wang, Zhipeng Chen, Xiaojing Shi, Qin Jiang, Cong Cao, Yun Zuo
BACKGROUND/AIMS: Lymphocyte antigen 6 complex, locus E (LY6E) is a member of the lymphostromal cell membrane Ly6 superfamily protein. The present study investigated the clinical significance and potential biological function of LY6E in gastric cancer (GC). METHODS: LY6E mRNA and protein expressions in human GC tissues and GC cells were tested. Relationship between LY6E expression and the GC patients' clinicopathologic characteristics was analyzed. LY6E was silenced by siRNA in the cultured GC cells...
February 9, 2018: Cellular Physiology and Biochemistry
Saife Niaz
Small RNAs govern almost every biological process in eukaryotes associating with the Argonaute proteins to form the RNA-induced silencing complex (mRISC). Argonaute proteins constitute the core of RISCs with different members having variety of protein binding partners and biochemical properties. This review focuses on the AGO subfamily of the Argonautes that are ubiquitously expressed and are associated with small RNAs. The structure, function and the role of the AGO proteins in the cell is discussed in detail...
November 27, 2017: Biological Chemistry
Mariya M Kucherenko, Halyna R Shcherbata
Stress can be temporary or chronic, and mild or acute. Depending on its extent and severity, cells either alter their metabolism, and adopt a new state, or die. Fluctuations in environmental conditions occur frequently, and such stress disturbs cellular homeostasis, but in general, stresses are reversible and last only a short time. There is increasing evidence that regulation of gene expression in response to temporal stress happens post-transcriptionally in specialized subcellular membrane-less compartments called ribonucleoprotein (RNP) granules...
February 14, 2018: Journal of Cell Science
Liping Yang, Rong Wang, Shixing Yang, Zexu Ma, Shaoli Lin, Yuchen Nan, Qisheng Li, Qiyi Tang, Yan-Jin Zhang
Movement of macromolecules between the cytoplasm and the nucleus occurs through the nuclear pore complex (NPC). Karyopherins comprise a family of soluble transport factors facilitating nucleocytoplasmic translocation of proteins through the NPC. In this study, we discovered that karyopherin alpha6 (KPNA6, also known as importin alpha7) was required for the optimal replication of porcine reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which are positive-sense, single-stranded RNA viruses replicating in the cytoplasm...
February 14, 2018: Journal of Virology
Yuling Nie, Tao Lang
AIM: The ATR-interacting protein (ATRIP) is responsible for the recognition of DNA damage-induced structure and regulation of cellular responses to DNA damage and replication stress. The purpose of our study was to identify the underlying mechanism with respect to chromatin loading and phosphorylation of ATRIP in mantle cell lymphoma (MCL). METHODS: JeKo cells were used in our study. Differently tagged ATRIP (Myc-, hemaglutinin (HA) or Flag) and minichromosome maintenance (MCM) complex (MCM2, MCM3, MCM5, and MCM6) were transfected into 293T cells...
November 1, 2017: Die Pharmazie
Carolyn M Klinge
The human genome is 'pervasively transcribed' leading to a complex array of non-coding RNAs (ncRNAs) that far outnumber coding mRNAs. ncRNAs have regulatory roles in transcription and post-transcriptional processes as well numerous cellular functions that remain to be fully described. Best characterized of the 'expanding universe' of ncRNAs are the ~ 22 nucleotide microRNAs (miRNAs) that base-pair to target mRNA's 3' untranslated region within the RNA-induced silencing complex (RISC) and block translation and may stimulate mRNA transcript degradation...
February 12, 2018: Endocrine-related Cancer
Masashi Fukuoka, Hirohiko Hohjoh
MicroRNAs (miRNAs) are functional small noncoding RNAs that work as mediators in gene silencing and that play important roles in gene regulation. A number of miRNAs have been found and their expression profiles have been examined by means of various microarray systems and real-time polymerase chain reaction (PCR) systems. Conventional microarrays as well as real-time PCR are able to detect existing miRNAs, in which inactive miRNAs that hardly contribute to gene silencing may be also contained. Here, we describe a comprehensive miRNA bioassay system with reporter genes for the detection of active miRNAs that are present in the RNA-induced silencing complexes, and actually working as mediators in gene silencing...
2018: Methods in Molecular Biology
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