Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA
Schmid, T. ; Snoek, L.B. ; Fröhli, E. ; Bent, M.L. van der; Kammenga, J.E. ; Hajnal, A. - \ 2015
Plos Genetics 11 (2015)5. - ISSN 1553-7404 - 16 p.
caenorhabditis-elegans - c-elegans - natural variation - vulvar induction - complex disease - receptor - protein - gene - kinase - activation
Human cancer is caused by the interplay of mutations in oncogenes and tumor suppressor genes and inherited variations in cancer susceptibility genes. While many of the tumor initiating mutations are well characterized, the effect of genetic background variation on disease onset and progression is less understood. We have used C. elegans genetics to identify genetic modifiers of the oncogenic RAS/MAPK signaling pathway. Quantitative trait locus analysis of two highly diverged C. elegans isolates combined with allele swapping experiments identified the polymorphic monoamine oxidase A (MAOA) gene amx-2 as a negative regulator of RAS/MAPK signaling. We further show that the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), which is a product of MAOA catalysis, systemically inhibits RAS/MAPK signaling in different organs of C. elegans. Thus, MAOA activity sets a global threshold for MAPK activation by controlling 5-HIAA levels. To our knowledge, 5-HIAA is the first endogenous small molecule that acts as a systemic inhibitor of RAS/MAPK signaling.
Loss-of-function of b-catenin bar-1 slows development and activates the Wnt pathway in Caenorhabditis elegans
Bent, M.L. van der; Sterken, M.G. ; Volkers, J.M. ; Riksen, J.A.G. ; Schmid, T. ; Hajnal, A. ; Kammenga, J.E. ; Snoek, L.B. - \ 2014
Scientific Reports 4 (2014). - ISSN 2045-2322 - 7 p.
natural variation data - c-elegans - signaling components - neuroblast migration - negative regulator - vulval development - gene-expression - cell-migration - proteins - endoderm
C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling components are known. Four beta-catenins are important gene expression regulators in Wnt-signalling. One of these, bar-1, is part of the canonical Wnt-pathway. Together with Wnt effector pop-1, bar-1 forms a transcription activation complex which regulates the transcription of downstream genes. The effects of bar-1 loss-of-function mutations on many phenotypes have been studied well. However, the effects on global gene expression are unknown. Here we report the effects of a loss-of-function mutation bar-1(ga80). By analysing the transcriptome and developmental phenotyping we show that bar-1(ga80) impairs developmental timing. This developmental difference confounds the comparison of the gene expression profile between the mutant and the reference strain. When corrected for this difference it was possible to identify genes that were directly affected by the bar-1 mutation. We show that the Wnt-pathway itself is activated, as well as transcription factors elt-3, pqm-1, mdl-1 and pha-4 and their associated genes. The outcomes imply that this response compensates for the loss of functional bar-1. Altogether we show that bar-1 loss-of function leads to delayed development possibly caused by an induction of a stress response, reflected by daf-16 activated genes.
Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension
Doroszuk, A. ; Jonker, M.J. ; Pul, N. ; Breit, T.M. ; Zwaan, B.J. - \ 2012
BMC Genomics 13 (2012). - ISSN 1471-2164
genome-wide - starvation resistance - expression patterns - caloric restriction - dietary restriction - c-elegans - caenorhabditis-elegans - laboratory selection - oxidative stress - immune-response
Background While studying long-lived mutants has advanced our understanding of the processes involved in ageing, the mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown. Here, we characterise genome-wide expression patterns of a long-lived, natural variant of Drosophila melanogaster resulting from selection for starvation resistance (SR) and compare it with normal-lived control flies (C). We do this at two time points representing middle age (90% survival) and old age (10% survival) respectively, in three adult diets (malnutrition, optimal food, and overfeeding). Results We found profound differences between Drosophila lines in their age-related expression. Most of the age-associated changes in normal-lived flies were abrogated in long-lived Drosophila. The stress-related genes, including those involved in proteolysis and cytochrome P450, were generally higher expressed in SR flies and showed a smaller increase in expression with age compared to C flies. The genes involved in reproduction showed a lower expression in middle-aged SR than in C flies and, unlike C flies, a lack of their downregulation with age. Further, we found that malnutrition strongly affected age-associated transcript patterns overriding the differences between the lines. However, under less stressful dietary conditions, line and diet affected age-dependent expression similarly. Finally, we present lists of candidate markers of ageing and lifespan extension. Conclusions Our study unveils transcriptional changes associated with lifespan extension in SR Drosophila. The results suggest that natural genetic variation for SR and lifespan can operate through similar transcriptional mechanisms as those of dietary restriction and life-extending mutations. Keywords: Ageing; Gene expression; Microarray; Drosophila melanogaster; Natural variation; Diet
Ecology and Evolution of Soil Nematode Chemotaxis
Rasmann, S. ; Ali, J.G. ; Helder, J. ; Putten, W.H. van der - \ 2012
Journal of Chemical Ecology 38 (2012)6. - ISSN 0098-0331 - p. 615 - 628.
plant-parasitic nematodes - root-feeding caterpillars - host search strategies - potato cyst nematodes - entomopathogenic nematodes - meloidogyne-incognita - natural enemies - c-elegans - phylogenetic-relationships - globodera-rostochiensis
Plants influence the behavior of and modify community composition of soil-dwelling organisms through the exudation of organic molecules. Given the chemical complexity of the soil matrix, soil-dwelling organisms have evolved the ability to detect and respond to these cues for successful foraging. A key question is how specific these responses are and how they may evolve. Here, we review and discuss the ecology and evolution of chemotaxis of soil nematodes. Soil nematodes are a group of diverse functional and taxonomic types, which may reveal a variety of responses. We predicted that nematodes of different feeding guilds use host-specific cues for chemotaxis. However, the examination of a comprehensive nematode phylogeny revealed that distantly related nematodes, and nematodes from different feeding guilds, can exploit the same signals for positive orientation. Carbon dioxide (CO2), which is ubiquitous in soil and indicates biological activity, is widely used as such a cue. The use of the same signals by a variety of species and species groups suggests that parts of the chemo-sensory machinery have remained highly conserved during the radiation of nematodes. However, besides CO2, many other chemical compounds, belonging to different chemical classes, have been shown to induce chemotaxis in nematodes. Plants surrounded by a complex nematode community, including beneficial entomopathogenic nematodes, plant-parasitic nematodes, as well as microbial feeders, are thus under diffuse selection for producing specific molecules in the rhizosphere that maximize their fitness. However, it is largely unknown how selection may operate and how belowground signaling may evolve. Given the paucity of data for certain groups of nematodes, future work is needed to better understand the evolutionary mechanisms of communication between plant roots and soil biota
Aging Uncouples Heritability and Expression-QTL in Caenorhabditis elegans
Viñuela Rodriguez, A. ; Snoek, L.B. ; Riksen, J.A.G. ; Kammenga, J.E. - \ 2012
G3 : Genes Genomes Genetics 2 (2012)5. - ISSN 2160-1836 - p. 597 - 605.
quantitative trait loci - cdna microarray data - life-history traits - gene-expression - c-elegans - age - arabidopsis - genomics - normalization - plasticity
The number and distribution of gene expression QTL (eQTL) represent the genetic architecture of many complex traits, including common human diseases. We previously reported that the heritable eQTL patterns are highly dynamic with age in an N2 × CB4856 recombinant inbred population of the nematode Caenorhabditis elegans. In particular, we showed that the number of eQTL decreased with age. Here, we investigated the reason for this decrease by combining gene expression profiles at three ages in the wild types N2 and CB4856 with the reported expression profiles of the RIL population. We determined heritability and transgression (when gene expression levels in the RILs are more extreme than the parents) and investigated their relation with eQTL changes with age. Transgressive segregation was widespread but depended on physiological age. The percentage of genes with an eQTL increased with a higher heritability in young worms. However, for old worms this percentage hardly increased. Using a single marker approach, we found that almost 20% of genes with heritability >0.9 had an eQTL in developing worms. Surprisingly, only 10% was found in old worms. Using a multimarker approach, this percentage increased to almost 30% for both age groups. Comparison of the single marker to a multiple marker eQTL mapping indicated that heritable regulation of gene expression becomes more polygenic in aging worms due to multiple loci and possible epistatic interactions. We conclude that linkage studies should account for the relation between increased polygenic regulation and diminished effects at older ages.
Gene Expression Modifications by Temperature-Toxicants Interactions in Caenorhabditis elegans
Vinuela Rodriguez, A. ; Snoek, L.B. ; Riksen, J.A.G. ; Kammenga, J.E. - \ 2011
PLoS ONE 6 (2011)9. - ISSN 1932-6203 - 11 p.
zebrafish-danio-rerio - cdna microarray data - organophosphorus pesticides - developmental neurotoxicity - chemical-mixtures - binary-mixtures - heat-stress - c-elegans - toxicity - chlorpyrifos
Although organophosphorus pesticides (OP) share a common mode of action, there is increased awareness that they elicit a diverse range of gene expression responses. As yet however, there is no clear understanding of these responses and how they interact with ambient environmental conditions. In the present study, we investigated genome-wide gene expression profiles in the nematode Caenorhabditis elegans exposed to two OP, chlorpyrifos and diazinon, in single and combined treatments at different temperatures. Our results show that chlorpyrifos and diazinon induced expression of different genes and that temperature affected the response of detoxification genes to the pesticides. The analysis of transcriptional responses to a combination of chlorpyrifos and diazinon shows interactions between toxicants that affect gene expression. Furthermore, our combined analysis of the transcriptional responses to OP at different temperatures suggests that the combination of OP and high temperatures affect detoxification genes and modified the toxic levels of the pesticides
A genome-wide library of CB4856/N2 introgression lines of Caenorhabditis elegans
Doroszuk, A. ; Snoek, L.B. ; Fradin, E. ; Riksen, J.A.G. ; Kammenga, J.E. - \ 2009
Nucleic acids research 37 (2009)16. - ISSN 0305-1048 - p. e110 - e110.
quantitative trait locus - life-history traits - genotype-environment interactions - natural variation - c-elegans - consomic strains - complex traits - qtl - architecture - polymorphism
Recombinant inbred lines (RILs) derived from Caenorhabditis elegans wild-type N2 and CB4856 are increasingly being used for mapping genes underlying complex traits. To speed up mapping and gene discovery, introgression lines (ILs) offer a powerful tool for more efficient QTL identification. We constructed a library of 90 ILs, each carrying a single homozygous CB4856 genomic segment introgressed into the genetic background of N2. The ILs were genotyped by 123 single-nucleotide polymorphism (SNP) markers. The proportion of the CB4856 segments in most lines does not exceed 3%, and together the introgressions cover 96% of the CB4856 genome. The value of the IL library was demonstrated by identifying novel loci underlying natural variation in two ageing-related traits, i.e. lifespan and pharyngeal pumping rate. Bin mapping of lifespan resulted in six QTLs, which all have a lifespan-shortening effect on the CB4856 allele. We found five QTLs for the decrease in pumping rate, of which four colocated with QTLs found for average lifespan. This suggests pleiotropic or closely linked QTL associated with lifespan and pumping rate. Overall, the presented IL library provides a versatile resource toward easier and efficient fine mapping and functional analyses of loci and genes underlying complex traits in C. elegans
In silico miRNA prediction in metazoan genomes: balancing between sensitivity and specificity
Burgt, A. van der; Fiers, M.W.E.J. ; Nap, J.P.H. ; Ham, R.C.H.J. van - \ 2009
BMC Genomics 10 (2009). - ISSN 1471-2164 - 24 p.
messenger-rna targets - computational identification - microrna precursors - sequence database - folding measures - c-elegans - hairpins - reveals - genes - classification
Background - MicroRNAs (miRNAs), short ~21-nucleotide RNA molecules, play an important role in post-transcriptional regulation of gene expression. The number of known miRNA hairpins registered in the miRBase database is rapidly increasing, but recent reports suggest that many miRNAs with restricted temporal or tissue-specific expression remain undiscovered. Various strategies for in silico miRNA identification have been proposed to facilitate miRNA discovery. Notably support vector machine (SVM) methods have recently gained popularity. However, a drawback of these methods is that they do not provide insight into the biological properties of miRNA sequences. Results - We here propose a new strategy for miRNA hairpin prediction in which the likelihood that a genomic hairpin is a true miRNA hairpin is evaluated based on statistical distributions of observed biological variation of properties (descriptors) of known miRNA hairpins. These distributions are transformed into a single and continuous outcome classifier called the L score. Using a dataset of known miRNA hairpins from the miRBase database and an exhaustive set of genomic hairpins identified in the genome of Caenorhabditis elegans, a subset of 18 most informative descriptors was selected after detailed analysis of correlation among and discriminative power of individual descriptors. We show that the majority of previously identified miRNA hairpins have high L scores, that the method outperforms miRNA prediction by threshold filtering and that it is more transparent than SVM classifiers. Conclusion - The L score is applicable as a prediction classifier with high sensitivity for novel miRNA hairpins. The L-score approach can be used to rank and select interesting miRNA hairpin candidates for downstream experimental analysis when coupled to a genome-wide set of in silico-identified hairpins or to facilitate the analysis of large sets of putative miRNA hairpin loci obtained in deep-sequencing efforts of small RNAs. Moreover, the in-depth analyses of miRNA hairpins descriptors preceding and determining the L score outcome could be used as an extension to miRBase entries to help increase the reliability and biological relevance of the miRNA registry
Beyond induced mutants: using worms to study natural variation in genetic pathways
Kammenga, J.E. ; Philips, P.C. ; Bono, M. de; Doroszuk, A. - \ 2008
Trends in Genetics 24 (2008)4. - ISSN 0168-9525 - p. 178 - 185.
quantitative trait loci - life-history traits - genotype-environment interactions - single-nucleotide polymorphisms - nematode caenorhabditis-elegans - c-elegans - linkage disequilibrium - genus caenorhabditis - wild populations - expression
Induced mutants in the nematode Caenorhabditis elegans are used to study genetic pathways of processes ranging from aging to behavior. The effects of such mutations are usually analyzed in a single wildtype background: N2. However, studies in other species demonstrate that the phenotype(s) of induced mutations can vary widely depending on the genetic background. Moreover, induced mutations in one genetic background do not reveal the allelic effects that segregate in natural populations and contribute to phenotypic variation. Because other wildtype Caenorhabditis spp., including C. elegans, are now available, we review how current mapping resources and methodologies within and between species support the use of Caenorhabditis spp. for studying genetic variation, with a focus on pathways associated with human disease.
A Caenorhabditis elegans Wild Type Defies the Temperature-Size Rule Owing to a Single Nucleotide Polymorphism in tra-3
Kammenga, J.E. ; Doroszuk, A. ; Riksen, J.A.G. ; Hazendonk, E. ; Spiridon, L.N. ; Petrescu, A.J. ; Tijsterman, M. ; Plasterk, R.H.A. ; Bakker, J. - \ 2007
Plos Genetics 3 (2007)3. - ISSN 1553-7404
quantitative trait loci - secondary structure prediction - life-history puzzle - drosophila-melanogaster - body-size - cell-size - c-elegans - transcription factor - sex-determination - cold-acclimation
Ectotherms rely for their body heat on surrounding temperatures. A key question in biology is why most ectotherms mature at a larger size at lower temperatures, a phenomenon known as the temperature¿size rule. Since temperature affects virtually all processes in a living organism, current theories to explain this phenomenon are diverse and complex and assert often from opposing assumptions. Although widely studied, the molecular genetic control of the temperature¿size rule is unknown. We found that the Caenorhabditis elegans wild-type N2 complied with the temperature¿size rule, whereas wild-type CB4856 defied it. Using a candidate gene approach based on an N2 × CB4856 recombinant inbred panel in combination with mutant analysis, complementation, and transgenic studies, we show that a single nucleotide polymorphism in tra-3 leads to mutation F96L in the encoded calpain-like protease. This mutation attenuates the ability of CB4856 to grow larger at low temperature. Homology modelling predicts that F96L reduces TRA-3 activity by destabilizing the DII-A domain. The data show that size adaptation of ectotherms to temperature changes may be less complex than previously thought because a subtle wild-type polymorphism modulates the temperature responsiveness of body size. These findings provide a novel step toward the molecular understanding of the temperature¿size rule, which has puzzled biologists for decades.
Environmental influence on the genetic correlations between life-history traits in Caenorhabditis elegans
Gutteling, E.W. ; Doroszuk, A. ; Riksen, J.A.G. ; Prokop, Z. ; Reszka, J. ; Kammenga, J.E. - \ 2007
Heredity 98 (2007)4. - ISSN 0018-067X - p. 206 - 213.
phenotypic plasticity - offspring size - trade-offs - egg-size - arabidopsis-thaliana - seed beetle - c-elegans - wild-type - loci - pleiotropy
Empirical evidence is mounting to suggesting that genetic correlations between life-history traits are environment specific. However, detailed knowledge about the loci underlying genetic correlations in different environments is scant. Here, we studied the influence of temperature (12°C and 24°C) on the genetic correlations between egg size, egg number and body mass in the nematode Caenorhabditis elegans. We used a quantitative trait loci (QTL) approach based on a genetic map with evenly spaced single nucleotide polymorphism markers in an N2 CB4856 recombinant inbred panel. Significant genetic correlations between various traits were found at both temperatures. We detected pleiotropic or closely linked QTL, which supported the negative correlation between egg size and egg number at 12°C, the positive correlation across temperatures for body mass, and the positive correlation between body mass and egg size at 12°C. The results indicate that specific loci control the covariation in these life-history traits and the locus control is prone to environmental conditions
The diverse roles of transverse filaments of synaptonemal complexes in meiosis
Boer, E. de; Heyting, C. - \ 2006
Chromosoma 115 (2006)3. - ISSN 0009-5915 - p. 220 - 234.
double-strand breaks - meiotic crossing-over - sister-chromatid cohesion - dna mismatch-repair - crossover interference - chromosome synapsis - saccharomyces-cerevisiae - c-elegans - recombination nodules - holliday junctions
In most eukaryotes, homologous chromosomes (homologs) are closely apposed during the prophase of the first meiotic division by a ladderlike proteinaceous structure, the synaptonemal complex (SC) [Fawcett, J Biophys Biochem Cytol 2:403-406, 1956; Moses, J Biophys Biochem Cytol 2:215-218, 1956]. SCs consist of two proteinaceous axes, which each support the two sister chromatids of one homolog, and numerous transverse filaments (TFs), which connect the two axes. Organisms that assemble SCs perform meiotic recombination in the context of these structures. Although much information has accumulated about the composition of SCs and the pathways of meiotic crossing over, several questions remain about the role of SCs in meiosis, in particular, about the role of the TFs. In this review, we focus on possible role(s) of TFs. The interest in TF functions received new impulses from the recent characterization of TF-deficient mutants in a number of species. Intriguingly, the phenotypes of these mutants are very different, and a variety of TF functions appear to be hidden behind a facade of morphological conservation. However, in all TF-deficient mutants a specific class of crossovers that display interference is affected. TFs appear to create suitable preconditions for the formation of these crossovers in most species, but are most likely not directly involved in the interference process itself. Furthermore, TFs are important for full-length homolog alignment
Meiotic transverse filament proteins: essential for crossing over
Heyting, C. - \ 2005
Transgenic Research 14 (2005)5. - ISSN 0962-8819 - p. 547 - 550.
synaptonemal complex - c-elegans - crossover interference - synapsis - chromosomes - zip1 - recombination - organization - drosophila - molecules
Meiosis is a specialized set of two nuclear divisions, meiosis I and II, by which a diploid cell produces four haploid daughters. After premeiotic DNA replication, homologous chromosomes pair and recombine, and then disjoin at meiosis I. Subsequently, at meiosis II, the sister chromatids of each chromosome segregate. In nearly all eukaryotes, meiotic chromosome pairing culminates in the formation of a ladderlike supramolecular protein structure, the synaptonemal complex (SC) (Page and Hawley, 2004). The rungs of the ladder are known as transverse filaments (TFs). Genes encoding TF proteins have been identified in a limited number of organisms, and their function has been studied by mutational analysis. Although TF proteins show little amino acid sequence conservation, their structure and function are largely conserved. In all analyzed species, TF proteins are required for meiotic reciprocal recombination (crossing over).
Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination., and XY body formation
Vries, F.A.T. de; Boer, E. de; Bosch, M. ; Baarends, W.M. ; Ooms, M. ; Yuan, L. ; Liu, J.G. ; Zeeland, A.A. van; Heyting, C. ; Pastink, A. - \ 2005
Genes and Development 19 (2005)11. - ISSN 0890-9369 - p. 1376 - 1389.
double-strand breaks - mismatch repair proteins - chromosome synapsis - crossing-over - mammalian meiosis - axial elements - c-elegans - homolog - mice - localization
In meiotic prophase, synaptonemal complexes (SCs) closely appose homologous chromosomes (homologs) along their length. SCs are assembled from two axial elements (AEs), one along each homolog, which are connected by numerous transverse filaments (TFs). We disrupted the mouse gene encoding TF protein Sycp1 to analyze the role of TFs in meiotic chromosome behavior and recombination. Sycp1(-/-), mice are infertile, but otherwise healthy. Sycp1(-/-) spermatocytes form normal AEs, which align homologously, but do not synapse. Most Sycp1(-/-) spermatocytes arrest in pachynema, whereas a small proportion reaches diplonema, or, exceptionally, metaphase I. In leptotene Sycp1(-/-) spermatocytes, gamma H2AX (indicative of DNA damage, including double-strand breaks) appears normal. In pachynema, Sycp1(-/-) spermatocytes display a number of discrete gamma H2AX domains along each chromosome, whereas gamma H2AX disappears from autosomes in wild-type spermatocytes. RAD51/DMC1, RPA, and MSH4 foci (which mark early and intermediate steps in pairing/recombination) appear in similar numbers as in wild type, but do not all disappear, and MLH1 and MLH3 foci (which mark late steps in crossing over) are not formed. Crossovers were rare in metaphase I of Sycp1(-/-) mice. We propose that SYCP1 has a coordinating role, and ensures formation of crossovers. Unexpectedly, Sycp1(-/-) spermatocytes did not form XY bodies.
Modelling nematode life cycles using dynamic energy budgets
Jager, T. ; Alda Alvarez, O. ; Kammenga, J.E. ; Kooijman, S.A.L.M. - \ 2005
Functional Ecology 19 (2005)1. - ISSN 0269-8463 - p. 136 - 144.
caenorhabditis-elegans - toxicity tests - daphnia-magna - c-elegans - growth - reproduction - briggsae - strategy
1. To understand the life cycle of an organism, it is important to understand the underlying physiological mechanisms of their life histories. We here use the theory of dynamic energy budgets (DEB) to investigate the close relationships between growth, reproduction and respiration in nematodes. 2. Using a set of simplified equations based on DEB theory, we are able to accurately describe life-cycle data from the literature for the free-living bacterivorous nematodes Caenorhabditis elegans, C. briggsae and Acrobeloides nanus, under different temperature or food regimes. 3. Nematodes apparently differ from other animals, as the initial growth is slower than expected. We explain this phenomenon by food limitation in the larvae, which is supported by more detailed physiological studies. 4. Food density and temperature are shown to have predictable effects on the growth curves (temperature affects only growth rate, whereas food density also affects ultimate size), although the reproduction patterns reveal some deviations from model predictions. 5. The presented model integrates the different aspects of the life cycle into a single framework, and can be applied as such to interpret the effects of various stressors
The influenza A virus NS1 protein binds small interfering RNAs and suppresses RNA silencing in plants
Bucher, E.C. ; Hemmes, J.C. ; Haan, P. de; Goldbach, R.W. ; Prins, M.W. - \ 2004
Journal of General Virology 85 (2004)4. - ISSN 0022-1317 - p. 983 - 991.
double-stranded-rna - translation initiation-factor - nicotiana-benthamiana - messenger-rna - transgenic plants - gene-expression - coat protein - human-cells - c-elegans - targets
RNA silencing comprises a set of sequence-specific RNA degradation pathways that occur in a wide range of eukaryotes, including animals, fungi and plants. A hallmark of RNA silencing is the presence of small interfering RNA molecules (siRNAs). The siRNAs are generated by cleavage of larger double-stranded RNAs (dsRNAs) and provide the sequence specificity for degradation of cognate RNA molecules. In plants, RNA silencing plays a key role in developmental processes and in control of virus replication. It has been shown that many plant viruses encode proteins, denoted RNA silencing suppressors, that interfere with this antiviral response. Although RNA silencing has been shown to occur in vertebrates, no relationship with inhibition of virus replication has been demonstrated to date. Here we show that the NS1 protein of human influenza A virus has an RNA silencing suppression activity in plants, similar to established RNA silencing suppressor proteins of plant viruses. In addition, NS1 was shown to be capable of binding siRNAs. The data presented here fit with a potential role for NS1 in counteracting innate antiviral responses in vertebrates by sequestering siRNAs.