Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.30.2 (endonuclease)
18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viral infections are one of the major reasons for the huge economic losses in shrimp farming. The control of viral diseases in shrimp remains a serious challenge for the shrimp aquacultural industry, with major pathogens, such as the white spot syndrome virus, yellow head virus, Taura syndrome virus, hepatopancreatic parvovirus, and baculoviruses, being geographically widespread. In the absence of a true adaptive immune response system in invertebrates such as shrimp, one of the alternative and more specific approaches to counteract viral infections in shrimp could be the use of molecular-based gene transfer technologies, such as RNA interference (RNAi). The RNAi mechanism is initiated by double-stranded RNAs (dsRNAs), which are fragmented into shorter 21-23 nucleotides of short interfering RNAs (siRNAs) by a type III endonuclease, the Dicer. RNAi, which is mediated by small interfering RNA (siRNA), results in the sequence-specific post-transcriptional silencing of a target gene. This gene-silencing mechanism is universally conserved and is a well-known phenomenon that exists in many eukaryotes, including invertebrates. It has been recently extended to shrimp as an important potential tool in viral disease prevention. RNAi technology shows considerable promise as a therapeutic approach and efficient strategy for shrimp virus control in the aquaculture industry. Further progress in understanding the mechanism of siRNAs at the molecular level, as well as strategies to achieve their tightly regulated, stable, prolonged and tissue-specific expression in an effective manner, will definitely revolutionize therapeutic approaches for counteracting viral diseases of shrimp. In the present review, the recent development and potential use of RNAi in combating shrimp viral infections is discussed.
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PMID:Application of nucleic-acid-based therapeutics for viral infections in shrimp aquaculture. 1894 35

Spermatogenesis requires intact, fully competent Sertoli cells. Here, we investigate the functions of Dicer, an RNaseIII endonuclease required for microRNA and small interfering RNA biogenesis, in mouse Sertoli cell function. We show that selective ablation of Dicer in Sertoli cells leads to infertility due to complete absence of spermatozoa and progressive testicular degeneration. The first morphological alterations appear already at postnatal day 5 and correlate with a severe impairment of the prepubertal spermatogenic wave, due to defective Sertoli cell maturation and incapacity to properly support meiosis and spermiogenesis. Importantly, we find several key genes known to be essential for Sertoli cell function to be significantly down-regulated in neonatal testes lacking Dicer in Sertoli cells. Overall, our results reveal novel essential roles played by the Dicer-dependent pathway in mammalian reproductive function, and thus pave the way for new insights into human infertility.
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PMID:Sertoli cell Dicer is essential for spermatogenesis in mice. 1907 Nov 4

Ribonuclease III (RNase III) is a double-stranded (ds)-RNA-specific endonuclease that plays essential roles in the maturation and decay of coding and noncoding RNAs. Bacterial RNases III are structurally the simplest members of the RNase III family, which includes the eukaryotic orthologs Dicer and Drosha. High-resolution crystal structures of RNase III of the hyperthermophilic bacteria Aquifex aeolicus and Thermotoga maritima are available. A. aeolicus RNase III also has been cocrystallized with dsRNA or specific hairpin substrates. These structures have provided essential structural insight to the mechanism of dsRNA recognition and cleavage. However, comparatively little is known about the catalytic behaviors of A. aeolicus or T. maritima RNases III. This chapter provides protocols for the purification of A. aeolicus and T. maritima RNases III and also describes the preparation of artificial heterodimers of Escherichia coli RNase III, which are providing new insight on the subunit and domain interactions involved in dsRNA recognition and cleavage.
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PMID:New approaches to understanding double-stranded RNA processing by ribonuclease III purification and assays of homodimeric and heterodimeric forms of RNase III from bacterial extremophiles and mesophiles. 1916 41

RNA interference (RNAi) is used as a reverse-genetic tool to examine functions of a gene in different cellular processes including apoptosis. As key cellular proteins are inactivated during apoptosis, and as RNAi requires cooperation of many cellular proteins, we examined whether DNA vector-based RNAi would continue to function during apoptosis. The short hairpin RNA transcribed from the DNA vector is processed by Dicer-1 to form small interfering RNA that is incorporated in the RNA-induced silencing complex (RISC) to guide a sequence-specific silencing of the target mRNA. We report here that DNA vector-based RNAi of three different genes, namely poly(ADP-ribose) polymerase-1, p14(ARF) and lamin A/C are abrogated during apoptosis. The failure of DNA vector-based RNAi was not at the level of Ago-2 or RISC-mediated step of RNAi but due to catalytic inactivation of Dicer-1 on specific cleavage at the STTD(1476) and CGVD(1538) sites within its RNase IIIa domain. Using multiple approaches, caspase-3 was identified as the major caspase responsible for the cleavage and inactivation of Dicer-1. As Dicer-1 is also the common endonuclease required for formation of microRNA (miRNA) in mammalian cells, we observed decreased levels of mature forms of miR-16, miR-21 and let-7a. Our results suggest a role for apoptotic cleavage and inactivation of Dicer-1 in controlling apoptotic events through altered availability of miRNA.
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PMID:Abrogation of DNA vector-based RNAi during apoptosis in mammalian cells due to caspase-mediated cleavage and inactivation of Dicer-1. 1922 43

The RNase III endonuclease Dicer plays a key role in generation of microRNAs (miRs). We hypothesized that Dicer regulates cancer cell susceptibility to immune surveillance through miR processing. Indeed, Dicer disruption up-regulated intercellular cell adhesion molecule (ICAM)-1 and enhanced the susceptibility of tumor cells to antigen-specific lysis by cytotoxic T-lymphocytes (CTLs), while expression of other immunoregulatory proteins examined was not affected. Blockade of ICAM-1 inhibited the specific lysis of CTLs against Dicer-disrupted cells, indicating a pivotal role of ICAM-1 in the interaction between tumor cells and CTL. Both miR-222 and -339 are down-regulated in Dicer-disrupted cells and directly interacted with the 3' untranslated region (UTR) of ICAM-1 mRNA. Modulation of Dicer or these miRs inversely correlated with ICAM-1 protein expression and susceptibility of U87 glioma cells to CTL-mediated cytolysis while ICAM-1 mRNA levels remained stable. Immunohistochemical and in situ hybridization analyses of 30 primary glioblastoma tissues demonstrated that expression of Dicer, miR-222, or miR-339 was inversely associated with ICAM-1 expression. Taken together, Dicer is responsible for the generation of the mature miR-222 and -339, which suppress ICAM-1 expression on tumor cells, thereby down-regulating the susceptibility of tumor cells to CTL-mediated cytolysis. This study suggests development of novel miR-targeted therapy to promote cytolysis of tumor cells.
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PMID:Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. 2063 86

Dicer is an RNAse III endonuclease that is essential for the biogenesis of microRNAs and small interfering RNAs. These small RNAs post-transcriptionally regulate mRNA gene expression through several mechanisms to affect key cellular events including proliferation, differentiation and apoptosis. Recently, the role of Dicer function in female reproductive tissues has begun to be elucidated through the use of knockout mouse models. Loss of Dicer within ovarian granulosa cells, luteal tissue, oocyte, oviduct and, potentially, the uterus renders females infertile. This review discusses these early studies and other data describing the current understanding of microRNAs and small interfering RNAs in female reproduction.
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PMID:Role of Dicer in female fertility. 1964 95

Spermatogenesis is a strictly regulated process, at both the transcriptional and the posttranscriptional level, which allows continuous gamete production throughout adulthood. A novel mechanism of posttranscriptional control mediated by microRNAs (miRNAs) has lately emerged as an important regulator of spermatogenesis. miRNAs are endogenous, small, noncoding RNAs produced through a multistep enzymatic process, which involves the action of Dicer, an RNaseIII endonuclease. Here, we first present a short overview of classic posttranscriptional control during spermatogenesis, and then concentrate on recent findings that have unraveled the important role of miRNAs in male reproductive function. Particular focus is given to the in vivo role of miRNAs that has been demonstrated through the generation of Sertoli cell-specific or germ cell-specific Dicer knockouts, as well as the potential application of these findings in the treatment of human male infertility and the development of male contraceptives. It is anticipated that unraveling miRNA functions in the testis will further our understanding of the regulatory mechanisms of mammalian spermatogenesis.
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PMID:microRNAs in the testis: building up male fertility. 1987 96

Juxtaglomerular cells are highly specialized myoepithelioid granulated cells located in the glomerular afferent arterioles. These cells synthesize and release renin, which distinguishes them from other cells. How these cells maintain their identity, restricted localization, and fate is unknown and is fundamental to the control of BP and homeostasis of fluid and electrolytes. Because microRNAs may control cell fate via temporal and spatial gene regulation, we generated mice with a conditional deletion of Dicer, the RNase III endonuclease that produces mature microRNAs in cells of the renin lineage. Deletion of Dicer severely reduced the number of juxtaglomerular cells, decreased expression of the renin genes (Ren1 and Ren2), lowered plasma renin concentration, and decreased BP. As a consequence of the disappearance of renin-producing cells, the kidneys developed striking vascular abnormalities and prominent striped fibrosis. We conclude that microRNAs maintain the renin-producing juxtaglomerular cells and the morphologic integrity and function of the kidney.
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PMID:The microRNA-processing enzyme dicer maintains juxtaglomerular cells. 2005 48

Canonical primary microRNA (pri-miRNA) precursors are transcribed by RNA polymerase II and then processed by the Drosha endonuclease to generate approximately 60 nt pre-miRNA hairpins. Pre-miRNAs in turn are cleaved by Dicer to generate mature miRNAs. Previously, some short introns, called miRtrons, were reported to fold into pre-miRNA hairpins after splicing and debranching, and miRNAs can also be excised by Dicer cleavage of rare endogenous short hairpin RNAs. Here we report that the miRNAs encoded by murine gamma-herpesvirus 68 (MHV68) are also generated via atypical mechanisms. Specifically, MHV68 miRNAs are transcribed from RNA polymerase III promoters located within adjacent viral tRNA-like sequences. The resultant pri-miRNAs, which bear a 5' tRNA moiety, are not processed by Drosha but instead by cellular tRNase Z, which cleaves 3' to the tRNA to liberate pre-miRNA hairpins that are then processed by Dicer to yield the mature viral miRNAs.
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PMID:A mammalian herpesvirus uses noncanonical expression and processing mechanisms to generate viral MicroRNAs. 2012 62

Recent reports have demonstrated that Dicer, an RNase III endonuclease required for microRNA (miRNA) maturation, is aberrantly expressed in different types of cancer. Furthermore, Dicer has been reported to be regulated by the let-7 family of miRNA genes. We hypothesize that Dicer is aberrantly expressed in oral cancer cells due to altered expressions of let-7 and that Dicer contributes to the development and progression of the disease. Western blot examination of Dicer protein levels in four head and neck squamous cell carcinoma (HNSCC) cell lines, including two oral cancer cell lines, demonstrated that Dicer had between 4- and 24-fold higher expression levels when compared to normal human primary gingival epithelial cells. Furthermore, five of six oral cancer tissues analyzed by indirect immunofluorescence had increased Dicer protein expression, compared to normal gingival epithelial tissue. The Dicer mRNA levels were not found to correlate well with protein expression in the HNSCC cell lines, suggesting that Dicer protein expression was post-transcriptionally regulated. Analysis of let-7a and let-7b levels in HNSCC cell lines by real-time PCR demonstrated that let-7b, but not let-7a, was significantly reduced in the HNSCC cell lines compared to control cells. Lastly, transfection of oral cancer cells with chemically synthesized let-7b and small interfering RNAs targeting Dicer significantly inhibited cell proliferation up to 83% and >100%, respectively, as early as 3 days post-transfection. Together, these data demonstrate that elevated expression levels of Dicer in oral cancer cells correlate with downregulation of let-7b and increased cell proliferation.
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PMID:Overexpression of dicer as a result of reduced let-7 MicroRNA levels contributes to increased cell proliferation of oral cancer cells. 2023 82


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