Biology subjects

Simon, S.

Publications and source records attributed to Simon, S..

3 recordsLinked to original sources

bioRxiv2018

Base-pairing requirements for small RNA mediated gene silencing of recessive self incompatibility alleles in Arabidopsis halleri.

Small non-coding RNAs are central regulators of genome activity and stability. Their regulatory function typically involves sequence similarity with their target sites, but understanding the criteria by which they specifically recognize and regulate their targets across the genome remains a major challenge in the field, especially in the face of the diversity of silencing pathways involved. The dominance hierarchy among self-incompatibility alleles in Brassicaceae is controlled by interactions between a highly diversified set of small non-coding RNAs produced by dominant S-alleles and their corresponding target sites on recessive S-alleles. By controlled crosses, we created numerous heterozygous combinations of S-alleles in Arabidopsis halleri and developed an RT-qPCR assay to compare allele-specific transcript levels for the pollen determinant of self-incompatibility (SCR). This provides the unique opportunity to evaluate the precise base-pairing requirements for effective transcriptional regulation of this target gene. We found strong transcriptional silencing of recessive SCR alleles in all heterozygote combinations examined. A simple threshold model of base-pairing for the sRNA-target interaction captures most of the variation in SCR transcript levels. For a subset of S-alleles, we also measured allele-specific transcript levels of the determinant of pistil specificity (SRK) and found sharply distinct expression dynamics throughout flower development between SCR and SRK. In contrast to SCR, both SRK alleles were expressed at similar levels in the heterozygote genotypes examined, suggesting no transcriptional control of dominance for this gene. We discuss the implications for the evolutionary processes associated with the origin and maintenance of the dominance hierarchy among self-incompatibility alleles.

genetics↗

bioRxiv2018

CagY-dependent regulation of type IV secretion in Helicobacter pylori is associated with alterations in integrin binding

Strains of Helicobacter pylori that cause ulcer or gastric cancer typically express a type IV secretion system (T4SS) encoded by the cag pathogenicity island (PAI). CagY is an ortholog of VirB10 that, unlike other VirB10 orthologs, has a large middle repeat region (MRR) with extensive repetitive sequence motifs, which undergo CD4+ T cell-dependent recombination during infection of mice. Recombination in the CagY MRR reduces T4SS function, diminishes the host inflammatory response, and enables the bacteria to colonize at a higher density. Since CagY is known to bind human 5{beta}1 integrin, we tested the hypothesis that recombination in the CagY MRR regulates T4SS function by modulating binding to 5{beta}1 integrin. Using a cell-free microfluidic assay, we found that H. pylori binding to 5{beta}1 integrin under shear flow is dependent on the CagY MRR, but independent of the presence of the T4SS pili, which are only formed when H. pylori is in contact with host cells. Similarly, expression of CagY in the absence of other T4SS genes was necessary and sufficient for whole bacterial cell binding to 5{beta}1 integrin. Bacteria with variant cagY alleles that reduced T4SS function showed comparable reduction in binding to 5{beta}1 integrin, though CagY was still expressed on the bacterial surface. We speculate that cagY-dependent modulation of H. pylori T4SS function is mediated by alterations in binding to 5{beta}1 integrin, which in turn regulates the host inflammatory response so as to maximize persistent infection.\n\nIMPORTANCEInfection with H. pylori can cause peptic ulcers, and is the most important risk factor for gastric cancer, the third most common cause of cancer death worldwide. The major H. pylori virulence factor that determines whether infection causes disease or asymptomatic colonization is the type IV secretion system (T4SS), a sort of molecular syringe that injects bacterial products into gastric epithelial cells and alters host cell physiology. We previously showed that recombination in CagY, an essential T4SS component, modulates the function of the T4SS. Here we found that these recombination events produce parallel changes in specific binding to 5{beta}1 integrin, a host cell receptor that is essential for T4SS-dependent translocation of bacterial effectors. We propose that CagY-dependent binding to 5{beta}1 integrin acts like a molecular rheostat that alters T4SS function and modulates the host immune response to promote persistent infection.

microbiology↗

bioRxiv2017

Predicted sensory consequences of voluntary actions modulate amplitude and temporal dynamics of preceding readiness potentials

Self-generated, voluntary actions, are preceded by a slow negativity in the scalp electroencephalography (EEG) signal recorded from frontal regions (termed readiness potential; RP). This signal, and its lateralized subcomponent (LRP), is mainly regarded as preparatory motor activity associated with the forthcoming motor act. However, it is not clear whether this neural signature is associated with preparatory motor activity, expectation of its associated sensory consequences, or both. Here we recorded EEG data from 12 healthy subjects while they performed self-paced button presses with their right index and middle fingers. In one condition (motor+sound) these button-presses triggered a sound while in another (motor-only) they did not. Additionally, subjects passively listened to sounds delivered in expected timings (sound-only). We found that the RP amplitude (locked to time of button press) was significantly more negative in the motor+sound compared with motor-only conditions starting ~1.4 seconds prior to button press. Importantly, no signal negativity was observed prior to expected sound delivery in the sound-only condition. Thus, the differences in RP amplitude between motor+sound and motor-only conditions are beyond differences in mere expectation of a forthcoming auditory sound. No significant differences between the two conditions were obtained in the LRP component. Our results suggest that expected auditory consequences are encoded in the early phase of the RP preceding the voluntary actions that generate them.

neuroscience↗