Nomenclature and functions of RNA-directed RNA polymerases

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There is little relationship between eukaryotic RNA-directed RNA polymerases (RDRs), viral RNA-dependent RNA polymerases (RdRps) and DNA-dependent RNA polymerases, indicating that RDRs evolved as an independent class of enzymes early in evolution. In fungi, plants and several animal systems, RDRs play a key role in RNA-mediated gene silencing [post-transcriptional gene silencing (PTGS) in plants and RNA interference (RNAi) in non-plants] and are indispensable for heterochromatin formation, at least, in Schizosaccharomyces pombe and plants. Recent findings indicate that PTGS, RNAi and heterochromatin formation not only function as host defence mechanisms against invading nucleic acids but are also involved in natural gene regulation. RDRs are required for these processes, initiating a broad interest in this enzyme class.

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Identification of plant RNA-directed RNA polymerases

The activity of a plant RNA-directed RNA polymerase (RDR) was detected ∼35 years ago in a search for enzymes that catalyse the replication of plant RNA viruses [1]. Upon infection with a virus, RDR activity was elevated, pointing to the misleading conclusion that RDRs are involved in virus replication. It turns out that virus genomes are not amplified by plant RDRs but by virus-encoded RNA-dependent RNA polymerases (RdRps) 2, 3. In plants, six RDRs (RDR1–RDR6) are expressed (see below) but

Nomenclature of RNA-directed RNA polymerases

In view of the considerable advances in characterizing specific functions of RNA-directed RNA polymerases, the current nomenclature is outdated – the main purpose of this article is to propose an updated consistent terminology for this class of enzymes. Initial studies on an enzyme that transcribed RNA from RNA templates were published in 1963 10, 11. This enzyme, which was termed RNA-dependent RNA polymerase, was encoded by a phage and not by a plant. Its biological function is to replicate

Post-transcriptional and virus-induced gene silencing in plants

The discovery of PTGS 29, 30 and RNA-mediated virus resistance [31] in plants provided the first clues about the role of RDRs. PTGS was occasionally observed in plant lines carrying multiple copies of transgene constructs. In these lines, a dramatic decrease in the steady-state mRNA level was detected. Moreover, if the transgene shared homology with an endogene, expression of both genes was suppressed. This co-suppression phenomenon was post-transcriptional and based on a mechanism that we know

Concluding remarks

RDRs play an important role in different cellular processes. We are just beginning to understand the complexity of how these enzymes are implicated in the regulation of gene expression. They are involved in transcriptional, post-transcriptional and translational processes and act in the cytoplasm as well as in the nucleus. Extensive genetic and biochemical analysis will be necessary to further elucidate the mechanistic function and the protein structures of this class of RNA-producing enzymes.

Acknowledgements

A part of the work was supported by the German Research Society in the frame of the Priority Program ‘Epigenetics’ (DFG Schwerpunktprogramm, SPP 1129 Epigenetics) and by the EU Specific Target Research Program (STERP), FOSRAK (Proposal no.: 5120).

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