Summary Stringent control of the NF-κB and type I interferon pathways is critical to effective host immune responses, yet the molecular mechanisms that negatively regulate these pathways are poorly understood. Here we show that NLRC5, a member of the NOD-like protein family, can inhibit the IKK complex and RIG-I/MDA5 function. NLRC5 strongly inhibited NF-κB-dependent responses by interacting with IKKα/IKKβ and blocking their phosphorylation. It also interacted with RIG-I and MDA5, but not with MAVS, to potently inhibit RIG-I-like receptor-mediated type I interferon responses. Consistent with these observations, NLRC5-specific siRNA knockdown not only enhanced the activation of NF-κB and its responsive genes, TNF-α and IL-6, but also promoted type I interferon signaling and antiviral immunity. Our findings identify NLRC5 as a key negative regulator that blocks two central components of the NF-κB and type I interferon pathways, and hence is a pivotal element in the homeostatic control of the innate immune system.

The narrow sheath (ns) phenotype of maize is a duplicate factor trait conferred by mutations at the unlinked loci ns1 and ns2. Recessive mutations at each locus together confer the phenotypic deletion of a lateral compartment in maize leaves and leaf homologs. Previous analyses revealed that the mediolateral axis of maize leaves is comprised of at least two distinct compartments, and suggest a model whereby NS function is required to recruit leaf founder cells from a lateral compartment of maize meristems. Genomic clones of two maize homeodomain-encoding genes were isolated by homology to the WUSCHEL-related gene PRESSED FLOWER(PRS). PRS is required for lateral sepal development in Arabidopsis, although no leaf phenotype is reported. Co-segregation of the ns phenotype with multiple mutant alleles of two maize PRShomologs confirms their allelism to ns1 and ns2. Analyses of NS protein accumulation verify that the ns-R mutations are null alleles. ns transcripts are detected in two lateral foci within maize meristems, and in the margins of lateral organ primordia. Whereas ns1and ns2 transcripts accumulate to equivalent levels in shoot meristems of vegetative seedlings, ns2 transcripts predominate in female inflorescences. Previously undiscovered phenotypes in the pressed flower mutant support a model whereby the morphology of eudicot leaves and monocot grass leaves has evolved via the differential elaboration of upper versus lower leaf zones. A model implicating an evolutionarily conserved NS/PRS function during recruitment of organ founder cells from a lateral domain of plant meristems is discussed.

Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR) proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR). Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC), a nucleotide binding (NB-ARC) and a leucine rich repeat (LRR) domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

S. 2019. "A comprehensive genome variation map of melon identifies multiple domestication events and loci influencing agronomic traits". Nature Genetics.