ReviewHomology-dependent gene silencing in plants and fungi: a number of variations on the same theme
Introduction
Homology-dependent gene silencing (HDGS) as a result of the introduction of transgenes has been revealed in several organisms (reviewed in [1]). Gene silencing as a consequence of sequence duplications is particularly diffused among plant species. The introduction of transgenes in plants produces at least two different HDGS phenomena: post-transcriptional gene silencing (PTGS) and transcriptional gene silencing (TGS). In fungi, silencing as consequence of sequence duplication has revealed a more complex scenario comprising several different gene silencing mechanisms.
This short review focuses on recent advances in the field of HDGS that are beginning to resolve the puzzle of this intriguing phenomenon. A substantial part of this review is dedicated to HDGS in plants because of the numerous studies that have been carried out in plant systems. However, particular attention is also dedicated to HDGS in fungi for two main reasons: first, the great variety of HDGS phenomena in fungi provides the opportunity to discover unique new molecular mechanisms of gene silencing; and second, the suitability of fungi as model systems enables us to address fundamental questions about the general mechanism of gene silencing.
On the basis of the idea that different HDGS phenomena may have evolved from an ancestral mechanism as a host defense response to invading sequences, such as transposons and viruses, we aim in this review to highlight commonalties of HDGS in fungi and plants.
Section snippets
Transcriptional gene silencing in plants
In both TGS and PTGS, silenced genes are inactivated in trans since interacting homologous genes are usually unlinked and reside in different chromosomes. Differences between the two HDGS mechanisms are in the homologous sequences: PTGS requires homology between coding sequences of interacting genes, whereas TGS requires homology between promoters.
TGS is reminiscent of paramutation in which an inactive allele (paramutagenic) can induce silencing of another (paramutable) allele. A DNA–DNA
Post-transcriptional gene silencing in plants
TGS is reminiscent of the already described gene silencing phenomena paramutation, whereas the discovery of PTGS has revealed the existence of a completely new and also unexpected gene silencing phenomenon (reviewed in 11, 12, 13). In contrast to TGS, silenced genes affected by PTGS are normally transcribed, but their transcripts do not accumulate as a consequence of rapid degradation. Even though the exact mechanism of PTGS is unknown, several studies have begun to unravel important PTGS
Premeiotic gene inactivation in fungi: RIP and MIP
Although there are fewer studies of HDGS phenomena in fungi compared with studies of plant HDGS, they revealed the existence of a number of variations of the same phenomenon. The discovery of the repeat induced point mutation (RIP) mechanism in Neurospora crassa is the first reported example of HDGS triggered by artificially introduced DNA [29]. To date, N. crassa and Ascobolus immersus seem to be the only organisms able to count the number of homologous sequence repeats and to inactivate them
HDGS in fungi vegetative cycle
The most studied and best-characterized HDGS phenomenon in fungi is ‘quelling’ in N. crassa [36]. Quelling shows strong similarities with PTGS in plants: it acts at post-transcriptional level, it is triggered by duplicated coding sequences, and it is reversible when transgenes are removed. However, the most important similarity between PTGS and quelling is that both are mediated by a diffusible trans-acting molecule, which in Neurospora is able to mediate gene silencing between nuclei in
HGDSs as defense systems
It now commonly accepted that HDGS phenomena can be considered as mechanisms that have evolved as defense responses to invading DNA sequences such as transposons or virus RNA sequences (reviewed in [43]). Indeed, there are at least two clear indications of involvement of HDGS in defense. First, several reports pointed out that PTGS in plants is strictly linked to RNA virus resistance mechanisms 44, 45, 46. Second, in Drosophila HDGS, which has several similarities to PTGS in plants, has been
An ancestral HDGS mechanism?
On the basis that different HDGS phenomena have evolved from an ancestral mechanism to protect genomes from invasive sequences, it is conceivable that they could share common steps in their mode of action. Although superficially the various gene silencing mechanisms seem to be different, fundamental similarities can be identified. In almost all the HDGS models, DNA–DNA interactions between homologous sequences is considered to be a key step (Figure 1). However, the recognition mechanism of
Conclusions and future perspectives
The discovery of HDGS has opened new perspectives in the understanding of genome maintenance and invading genomic sequences protection as well as gene regulation. The impressive amounts of studies carried out during the past few years have begun to uncover the complex mechanisms of the enigmatic silencing phenomena. However, great efforts will be necessary for a fine understanding of the molecular mechanisms HDGS and the isolation of cellular factors involved in different silencing mechanisms
Acknowledgements
We thank A Pickford for revising the manuscript. This work was supported in part by grants from the Istituto Pasteur Fondazione Cenci Bolognetti, from the Ministero dell’ Universita’ e della Ricerca Scientifica e Tecnologica, and from European Union BIOTECH program.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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