Post-transcriptional gene-silencing: RNAs on the attack or on the defense?

Abstract

Post‐transcriptional gene‐silencing (PTGS) was first discovered in plants and results from the sequence‐specific degradation of RNA. Degradation can be activated by introducing transgenes, RNA viruses or DNA sequences that are homologous to expressed genes. A similar RNA degradation mechanism which is inducible by double‐stranded RNA (dsRNAs), has been discovered recently in vertebrates, invertebrates and protozoa. dsRNAs may also be potent activators of PTGS in plants. PTGS is not cell autonomous, suggesting the synthesis of sequence‐specific silencing signals which are not only moving through the plant but are also amplified and an RNA‐directed RNA Polymerase which has recently been cloned from various plant species is a candidate enzyme for amplifying silencing signals. The natural role of PTGS seems to be as a defence against plant viruses, so what first appeared to be RNAs on the attack may now be considered RNAs on the defense. BioEssays 22:520–531, 2000. © 2000 John Wiley & Sons, Inc.

Virus-encoded suppressor of posttranscriptional gene silencing targets a maintenance step in the silencing pathway

“…It was proposed that these short RNAs provide specificity for target RNA degradation through association with an RNaseIII-like enzyme (2,6). In plants, PTGS of transgenes is typically associated with methylation of nuclear DNA corresponding to the transcribed region of the target RNA, although transcription levels of the transgene are generally unaffected (1). In addition, systemic signaling to trigger PTGS at a distance can occur in plants, presumably through transport of a nucleic acid signal (7)(8)(9).…”

“…P osttranscriptional gene silencing (PTGS) or RNA interference occurs in a wide variety of organisms, including plants, animals, and fungi (1,2). The PTGS process involves recognition of a target RNA and initiation of a sequence-specific RNA degradation pathway in the cytoplasm.…”

“…The PTGS process involves recognition of a target RNA and initiation of a sequence-specific RNA degradation pathway in the cytoplasm. Targets for PTGS may be recognized because of the presence of extensive double-stranded RNA (dsRNA) structure or because of an aberrant feature of the RNA (1). Small RNAs of 21-23 nt, corresponding to both sense and antisense strands of the target, are consistently associated with PTGS (2-6).…”

Interference of hepatitis C virus RNA replication by short interfering RNAs

“…RNAi, which can function independently of IFNinduced pathways, is also effective in mammalian cells (33,(41)(42)(43). This suggests that plants and animals share a conserved antiviral mechanism leading to specific destruction of nonself dsRNA (44,45). RNAi interferes with the replication of a number of animal viruses including HIV-1, flock house virus (FHV), Rous sarcoma virus, dengue virus, and poliovirus (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56).…”

On RNA interference as template immunity

“…The viral dsRNA is cleaved by the Dicer enzyme to produce short but highly-specific RNA fragments called short interfering RNAs (Bernstein et al 2001). This induces an amplification cycle: The short interference RNA fragments are stabilized by the RISC proteins and play the role of template 'antibodies' in binding specifically to viral mRNAs (Sijen and Kooter 2000). The viral mRNAs are then either (i) targeted for degradation (Sontheimer and Carthew 2004) or alternatively, (ii) used to generate further templates with identical specificity, through a polymerization reaction (Lipardi et al 2001).…”