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IN THIS ISSUE

Positive and Negative Feedback Coordinate Regulation of Disease Resistance Gene Expression

neckardt{at}aspb.org

Plant disease Resistance (R) genes enable plants to recognize specific pathogens that carry corresponding Avirulence (Avr) genes and, upon recognition, initiate defense signaling pathways that result in disease resistance. There are five generally recognized classes of proteins encoded by plant R genes. Cf-X proteins carry a transmembrane domain and extracellular N-terminal leucine-rich repeat (LRR) region, Xa21-type proteins are similar to Cf-X proteins but carry an additional intercellular C-terminal kinase domain, and Pto-like proteins are cytoplasmic Ser/Thr kinases with a putative membrane-anchoring N-terminal myristoylation site. Arabidopsis RPW8, which is a small putative membrane-associated coiled-coil (CC) domain protein, constitutes a fourth class. Members of the largest class of R gene encode nucleotide binding site (NBS)-LRR proteins, which carry an LRR region at the C terminus and either a Toll/Interleukin 1 receptor (TIR) or a CC domain at the N terminus. The LRR region of NBS-LRR proteins likely is involved in pathogen recognition, whereas the TIR or CC N-terminal region is thought to function in downstream signaling (reviewed in Dangl and Jones, 2001).

NBS-LRR genes are abundant in plant genomes. For example, Meyers et al. (2003) identified 149 NBS-LRR genes in the Arabidopsis Col-0 genome. In addition, it appears that many R genes, if not most, are tightly linked in clusters within plant genomes. Hulbert et al. (2001) reviewed this phenomenon and noted that genetically linked alleles or clusters of genes have a greater possibility for recombination than simple loci composed of single genes. Therefore, clustering of R genes might contribute to the continued generation of novel resistance alleles through recombination, gene conversion, and unequal crossing over. There is strong evidence for diversifying selection acting on a number of complex R gene loci, such as in the Cf4/9 family in tomato (Parniske et al., 1997), Xa21 in rice (Wang et al., 1998), and Arabidopsis RPP13 (Rose et al., 2004) and RPP5 (Noël et al., 1999), to name just a few.

It is also thought that there are fitness costs associated with the expression of R genes and the activation of defense response pathways in the absence of a pathogen carrying the cognate Avr gene (Heil and Baldwin, 2002). For example, several mutations affecting the complex RPP5 locus in Arabidopsis cause enhanced disease resistance and dwarfism, which is thought to be the result of constitutive upregulation of defense responses (Yang and Hua, 2004). In this issue of The Plant Cell, Yi and Richards (pages 2929–2939) analyze the regulation of gene expression at the RPP5 locus in the Arabidopsis Col-0 accession. The results show that multiple R genes at this locus are coordinately regulated through both positive (transcriptional activation) and negative (RNA silencing) feedback mechanisms. These complex feedback loops may contribute to the optimization of defense responses both in terms of reducing fitness costs of defense signaling and enhancing the capacity for the induction of defense responses in response to pathogen attack.

The Col-0 RPP5 locus comprises seven TIR-NBS-LRR R genes, which are interspersed with three related sequences and two non-R genes (Noël et al., 1999). The R genes in this cluster are more highly similar to each other than to any other R gene in the Arabidopsis genome, suggesting that the cluster evolved through local duplication and rearrangements (Baumgarten et al., 2003; Meyers et al., 2003). At least two of the R genes at the RPP5 locus have a demonstrated role in plant disease resistance against fungal and bacterial pathogens. RPP4 confers resistance to downy mildew caused by the fungus Hyaloperonospora parasitica (formerly Peronospora parasitica) (van der Biezen et al., 2002), and SNC1 (for suppressor of npr1-1, constitutive 1) functions in resistance against multiple pathogens, including strains of bacterial Pseudomonas syringae and fungal H. parasitica.

The snc1 mutant carries a gain-of-function mutation affecting SNC1, and the mutant plants exhibit dwarfism, accumulation of high levels of salicylic acid (SA), and constitutive activation of both SA-dependent and SA-independent defense pathways (Zhang et al., 2003). Two other mutations mapped to the RPP5 locus, cpr1 and bal, display similar phenotypes and upregulation of SNC1 expression (Bowling et al., 1994; Stokes et al., 2002). Stokes and Richards (2002) showed that both the cpr1 and bal mutants exhibit phenotypic instability (reversion to the wild-type phenotype) in the presence of DNA-damaging agents, and bal and cpr1 alleles in F1 hybrids show a paramutation-like interaction (a high frequency of cpr1 reversion in the presence of bal).

Yi and Richards found that transgenic overexpression of SNC1 produces plants with a bal-like phenotype. Segregating progeny of the SNC1 overexpressors displayed three distinct phenotypes, wild type, bal-like, and stunted, in a 1:2:1 ratio, and the stunted plants reverted back to wild type within several weeks (delayed normal growth syndrome). The authors determined that these phenotypes were dependent on dosage of the SNC1 transgene. Yang and Hua (2004) had previously shown that SNC1 is positively regulated by SA accumulation. Yi and Richards therefore investigated the possibility of coordinated regulation of multiple R genes at the RPP5 locus and found that overexpression of SNC1 leads to upregulation of several other R genes in the RPP5 cluster.

Interestingly, for stunted phenotypes, coordinated suppression of the same genes was found to correlate with SNC1 expression at 5 weeks (after plants were released from stunting). This observation, together with the putative epigenetic instability of the bal and cpr1 mutations, led the authors to investigate the possibility that SNC1 and other similar R genes at the RPP5 locus might be regulated by RNA silencing.

RNA silencing is known to play an important role in plant defense systems. Posttranscriptional gene silencing of virus-encoded genes is thought to limit replication and spread of viral pathogens, and many viral plant pathogens encode suppressors of silencing (reviewed in Vance and Vaucheret, 2001). RNA silencing has also been linked to resistance of bacterial pathogens (Katiyar-Agarwal et al., 2006). Three separate large-scale small RNA cDNA sequencing studies have identified diverse small RNA species originating from the RPP5 locus, including the SNC1 gene (Nakano et al., 2006; Rajagopalan et al., 2006; Kasschau et al., 2007). Yi and Richards show that 21- to 24-nucleotide small RNAs are generated from RPP5 locus R gene transcripts and that sense and antisense transcripts are produced from SNC1 and a similar sequence at the RPP5 locus, which may form the double-stranded RNAs that would serve as a precursor for the generation of small RNAs. In addition, they show that SNC1 transcription is increased in dcl4 and ago1 mutants, which are defective in RNA silencing.

This work underscores the complexities of R gene evolution and regulation and further demonstrates how RNA silencing at a complex R gene locus may play an important role in optimizing plant response to pathogen attack. First, it may reduce the fitness cost associated with expression of multiple R genes in the absence of pathogen attack; secondly, it might allow for a fail-safe mechanism for deactivating repression of R genes in response to pathogens whose mode of attack targets RNA silencing pathways.

Coordinated upregulation of R genes within the cluster may be important if multiple genes are required for resistance. In the Arabidopsis RPP2 locus, two tandemly located R genes function interdependently, and both are required to initiate disease resistance against a Hyaloperonospora isolate (Sinapidou et al., 2004). Hulbert et al. (2001) noted several examples of R gene clusters that contain structurally unrelated genes involved in disease resistance. In tomato, the NBS-LRR gene Prf lies within the cluster of Pto-type kinase genes at the complex Pto locus, and Prf is required for Pto-mediated resistance to Pseudomonas isolates carrying AvrPto. In addition, coordinated regulation of genes within a cluster may provide the plant with a broader spectrum of resistance to diverse pathogens. In some cases, R gene clusters contain one or more unrelated R genes that confer resistance to diverse pathogens, as in the RPP5 cluster. In addition to pathogen-specific R gene–mediated plant defense pathways, plants possess general basal defense pathways that limit the growth and spread of diverse pathogens in plant tissues, and there is some degree of genetic overlap between specific and basal resistance responses (Dangl and Jones, 2001). Clustering of R genes with genes involved in basal defense and coordinated expression of genes within a cluster is a possible mechanism.

It is interesting to note that SNC1-dependent coordinated regulation of RPP5 locus genes is functional only in accessions that carry functional SNC1, such as Col-0. Comparative analysis between Col-0 and Landsberg erecta accessions suggests that the RPP5 locus has undergone rapid diversifying evolution that is maintained by frequency-dependent selection (Noël et al., 1999). The work of Yi and Richards highlights the potential importance of regulation of gene expression as a factor in the evolution of R gene clusters.

	Footnotes

 
www.plantcell.org/cgi/doi/10.1105/tpc.107.056226

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A Cluster of Disease Resistance Genes in Arabidopsis Is Coordinately Regulated by Transcriptional Activation and RNA Silencing

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Plant Cell 2007 19: 2929-2939. [Abstract] [Full Text]  

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