mRNA translation is not a prerequisite for small interfering RNA-mediated mRNA cleavage.

Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Differentiation (Impact Factor: 2.84). 08/2005; 73(6):287-93. DOI: 10.1111/j.1432-0436.2005.00029.x
Source: PubMed

ABSTRACT RNA interference constitutes a major means of eliminating mRNAs, yet how the small interfering RNAs (siRNA) within the RNA-induced silencing complex (RISC) finds its homologous target in the cell remains unknown. An attractive hypothesis is that RNA interference is linked to translation which allows RISC ready access to every translated mRNA. To test whether translation could direct siRNAs to mRNAs, chemical and biological inhibitors of translation and their effects on mRNA cleavage were tested. Our results show that mRNA degradation by siRNAs is not dependent on mRNA translation.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Currently one of the most promising approaches in development of cancer virotherapy is based on the ability of oncolytic viruses to selective infection and lysis of tumor cells. Aim. The goal of the study was to identify and evaluate perspective oncolytic viruses capable of selectively destroying human glioma cells. Patients and methods. Original GB2m, GA14m and GB22m glioma cell cultures derived from patients were used for evaluating in vitro oncolytic activity of some typical orthopoxviruses, adenoviruses and parvoviruses. Results. The oncolytic activity in the human glioma cell models was confirmed for LIVP and WR strains of vaccinia virus, Adel2 and Ad2del strains with deletions within E1B/55Kgene and derived from human adenoviruses type 2 and 5, respectively. Conclusions. We consider these oncolytic viruses as promising agents for the treatment of human malignant glioma.
    Vestnik Rossiĭskoĭ akademii meditsinskikh nauk / Rossiĭskaia akademiia meditsinskikh nauk 12/2013;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNAs (miRNAs) regulate a large proportion of mam- malian genes by hybridizing to targeted messenger RNAs (mRNAs) and down-regulating their translation into protein. Although much work has been done in the genome-wide computational prediction of miRNA genes and their target mRNAs, an open question is how to efficiently obtain functional miRNA targets from a large number of candidate miRNA targets predicted by existing computational algorithms. In this paper, we propose a novel Bayesian model and learning algorithm, GenMiR++ (Generative model for miRNA regulation), that accounts for patterns of gene expression using miRNA expression data and a set of candidate miRNA targets. A set of high-confidence functional miRNA targets are then obtained from the data using a Bayesian learning algorithm. Our model scores 467 high-confidence miRNA targets out of 1,770 targets obtained from TargetScanS in mouse at a false detection rate of 2.5%: several confirmed miRNA targets appear in our high-confidence set, such as the interactions between miR-92 and the signal transduction gene MAP2K4, as well as the relationship between miR-16 and BCL2, an anti-apoptotic gene which has been implicated in chronic lymphocytic leukemia. We present results on the robustness of our model showing that our learning algorithm is not sensitive to various perturbations of the data. Our high-confidence targets represent a significant increase in the number of miRNA targets and represent a starting point for a global understanding of gene regulation.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Double–stranded RNA (dsRNA) induces a sequence–specific silencing in eukaryotic cells. This silencing process beggins when long dsRNA is cleaved to 21 to 26 long small RNA by means of the RNAse III–type enzyme Dicer. These small dsRNA are included into silencing effector complexes, that are targeted to complementary sequences. Small RNA dependent gene silencing can be achieved by distinct mechanisms based depending mainly on the nature of target sequences and on the proteins present in the effector complex. The route of interference RNA (RNAi) begins when Dicer yields small interference RNA (siR–NA) that bind to complementary mRNA for its degradation, forming the RISC complex. siRNA are naturally formed from transposons and dsRNA viruses during its replication, as well as from other bidirectional transcribed repetitive sequences. Some of the enzymes thar are part of the RNAi machinery, including Dicer, are encoded by multigene families in many species, that also play a role in other mechanisms of RND–dependent gene silencing. MicroRNA's (miRNA) are other small RNA's that can induce gene silencing at the mRNA level. These are formed in a general manner when Dicer process hairpin structures resulting from the transcription of non–coding sequences from plant and animal genomes. miRNA's are integrated into a RISC–like complex, after which, depending on their degree of complementarity with target mRNA, can either repress translation or induce mRNA degradation. miRNA–dependent silencing is essential for the development of multicellular organisms. Artificial RNAi induction by means of siRNA or miRNA is being used as a tool to inactivate gene expression in culture cells and in living organisms. This review focuses on the progress in the understanding of the mechanisms involved in gene regulation by RNA in animals and details some current efforts to apply theses phenomena as a tool in research and in the therapeutic of human diseases.
    Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 08/2006; 58(4):335-349. · 0.31 Impact Factor