Viruses and RNA interference in mammalian cells

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interferes with the replication of an invading virus and also suppresses normal cell ribosome functioning, killing both the virus and the host cell. It happens, if response lasts for sufficient long time. Figure 1 Mechanism of IFN action. Functions of selected IFN-inducible protein - PKR. It takes place among the IFN-induced proteins believed to affect virus multiplication within a single cell. It inhibits initiation of translation by phosphorylating eIF-2a (Samuel, 2001). Other IFN-induced proteins, which affect virus replication within the cell, except PKR kinase, are the the 2’,5’-oligoadenylate synthetase (OAS) family (catalyze the synthesis of oligoadenylates) and RNase L nuclease (a latent endoribonuclease) - mediate RNA degradation; the family of Mx protein GTPases (Mx proteins are GTPases that belong to the superfamily of dynamin-like GTPases) – target viral nucleocapsids and inhibit RNA synthesis; and RNA-specific adenosine deaminase (ADAR) – edits double-stranded RNA by deamination of adenosine to yield inosine. Still they are not completely investigated. (Samuel, 2001) 6
RNAi The development of biotechnological methods of research in the last years made possible RNA interference to be discovered. RNAi is a regulatory mechanism, which silences genes degrading mRNA in a sequence-specific manner with help of small pieces of doublestranded RNAs: small or short interfering RNAs (siRNAs) and micro RNAs (miRNAs). It suppresses gene expression at the translation stage or by interfering the transcription of specific genes. RNAi has been observed in organisms as diverse as plants, protozoa, nematodes, fungi, insects, and mammals (Hu et al., 2004). This process takes an integral part in various eukaryotic functions such as viral defense, chromatin remodeling, genome rearrangement, developmental timing, brain morphogenesis and stem cell maintenance (MacRae et al., 2006). 2. RNA interference History of discovery The history of RNAi discovery started when scientists tried to compare the activity of silencing of antisense or sense single-stranded RNAs (ssRNAs) with their double-stranded RNA (dsRNA) hybrid in two types of experiments in 1990. First group of experiments was made to estimate antisense suppression for selective silencing of plant gene expression. In theory, antisense RNA encoded by a transgene should prevent translation of complementary mRNA of a plant gene into protein by basepairing to it. But the control “sense” transgene RNAs are unable to do it, because they can not basepair to mRNA. Hence, the silencing should not been observed, but surprisingly it was (Smith et al., 1990). The other type of experiments, has led to the conclusion that the expression of both introduced and homologous endogenous genes in petunia leaves was suppressed by introduction of a pigment-producing gene that was under a control of a powerful promoter. This phenomenon scientist called “co-suppression”. It was discovered while scientists made the efforts to enhance coloration of petunia flowers. They tried to overexpress a transgene that encoded a protein involved in a synthesis of pigments. However, it led to a partial or complete color loss. That was the result of “co-suppression” or coordinate silencing (Napoli et al., 1990; Van der Krol et al., 1990). “Co-suppression” also occurs at the post-transcriptional level. Such post-transcriptional gene silencing (PTGS) in plants is equivalent of RNAi. Posttranscriptional gene silencing is a mechanism involving dsRNA, nucleases, small RNAs and 7
Page 1 and 2: UNIVERSITY OF TARTU FACULTY OF SCIE
Page 3 and 4: ACRONYMS AND ABBREVIATIONS CrPV - C
Page 5: LITERATURE OVERVIEW 1. Intracellula
Page 9 and 10: Figure 3. RNAi mechanism. RNAi is t
Page 11 and 12: Figure 4. Dicer components. 2 helic
Page 13 and 14: Link between miRNA, siRNA and RNAi
Page 15 and 16: 3. RNAi as an antiviral defense in
Page 17 and 18: 4. RNA interference in mammals The
Page 19 and 20: diseases, including liver cirrhosis
Page 21 and 22: esponse by suppressing the activity
Page 23 and 24: CONCLUSIONS In the present bachelor
Page 25 and 26: REFERENCES Aagaard, L. and Rossi, J
Page 27 and 28: Gitlin, L., Karelsky, S. and Andino
Page 29 and 30: Li, W.X. and Ding, S.W., (2001) Vir
Page 31 and 32: Schütz, S. and Sarnow, P. (2006) I

Viruses and RNA interference in mammalian cells

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