Real-Time Monitoring of Key Gene Products Involved in Rice Photoperiodic Flowering

Flowering is an important biological process through which plants determine the timing of reproduction. In rice, florigen mRNA is induced more strongly when the day length is shorter than the critical day length through recognition of 30-min differences in the photoperiod. Grain number, plant height, and heading date 7 (Ghd7), which encodes a CCT-domain protein unique to monocots, has been identified as a key floral repressor in rice, and Heading date 1 (Hd1), a rice ortholog of the Arabidopsis floral activator CONSTANS (CO), is another key floral regulator gene. The Hd1 gene product has been shown to interact with the Ghd7 gene product to form a strong floral repressor complex under long-day conditions. However, the mRNA dynamics of these genes cannot explain the day-length responses of their downstream genes. Thus, a real-time monitoring system of these key gene products is needed to elucidate the molecular mechanisms underlying accurate photoperiod recognition in rice. Here, we developed a monitoring system using luciferase (LUC) fusion protein lines derived from the Ghd7-LUC and Hd1-LUC genes. We successfully obtained a functionally complemented gene-targeted line for Ghd7-LUC. Using this system, we found that the Ghd7-LUC protein begins to accumulate rapidly after dawn and reaches its peak more rapidly under a short-day condition than under a long-day condition. Our system provides a powerful tool for revealing the accurate time-keeping regulation system incorporating these key gene products involved in rice photoperiodic flowering.

Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden

Amplifications of oncogenic genes are often considered actionable. However, not all patients respond. Questions have therefore arisen regarding the degree to which amplifications, especially non-focal ones, mediate overexpression. We found that a subset of high-level gene amplifications (≥ 6 copies) (from The Cancer Genome Atlas database) was not over-expressed at the RNA level. Unexpectedly, focal amplifications were more frequently silenced than non-focal amplifications. Most non-focal amplifications were not silenced; therefore, non-focal amplifications, if over-expressed, may be therapeutically tractable. Furthermore, specific silencing of high-level focal or non-focal gene amplifications may explain resistance to drugs that target the relevant gene product.

Maximized redundant and synergistic information transfers predict the rise in the output gene expression noise in a generic class of coherent type-1 feed-forward loop networks

We apply the partial information decomposition principle to a generic coherent type-1 feed-forward loop (C1-FFL) motif with tunable direct and indirect transcriptional regulations of the output gene product and quantify the redundant, synergistic, and unique information transfers from the regulators to their target output species. Our results which are obtained within the small-noise regime of a Gaussian framework reveal that the redundant and synergistic information transfers are antagonistically related to the output noise. Most importantly, these two information flavors are maximized prior to the minimization and subsequent growth of the output noise. Therefore, we hypothesize that the dynamic information redundancy and synergy maxima may possibly be utilized as efficient statistical predictors to forecast the increasing trend of the fluctuations associated with the output gene expression dynamics in the C1-FFL class of network motifs. Our core analytical finding is supported by exact stochastic simulation data and furthermore validated for a diversified repertoire of biologically plausible parameters. Since, the output gene product serves essential physiological purposes in the cell, a predictive estimate of its noise level is supposed to be of considerable biophysical utility.

Gene modification research has potential, from diagnostic to therapeutic levels. The most promising metabolic pathways include the TGF-1 signaling system, inflammation and protein transport

A human disease modifier gene is a gene that regulates another gene's function or effects. The presence of a modifier gene is not sufficient to cause a disease. Nonetheless, the presence of a modifier gene alters the disease's onset and severity. A genetic modifier can interact in several ways with another gene product. Changes in penetration and expressiveness, direct interaction with the target gene product, mechanistic contribution to the same biological process and/or functional compensation through other routes might all have effects. Despite long hypothesized genetic modifiers, their influence is yet unclear. Improved computational tools, international consortia with larger patient cohorts, improved laboratory precision procedures, and high-throughput technology have all helped find and verify genetic modifiers in recent years. As new possible genetic modifiers are found, common pathways can be established linking some modifying genes or neuromuscular diseases. The most promising metabolic pathways include the TGF-1 signaling system, inflammation, endoplasmic reticulum metabolism, axon formation, regeneration, extracellular matrix, RNA metabolism and protein transport. Perhaps in the future, we will conceive of neuromuscular diseases in terms of impaired molecular processes and the amount involving multiple metabolic pathways, rather than main genetic variations or medical nomenclature. Another fascinating feature of genetic modifiers in neuromuscular diseases is the involvement of genetic moderators in oligogenic inheritance. Preliminary research on animal models and people indicates that more rare, non-synonymous mutations in NMD-related genes might worsen muscle damage and lead to a more severe phenotype. Besides oligogenic inheritance, the "diagnostic gap"—individuals who remain unresolved after exome or genome sequencing—can be explained by the action of genetic modifiers. In the coming years, genetic modification research is expected to advance from diagnostic to therapeutic levels, and it would be extremely tempting from a therapeutic point of view to identify "protective" modifiers and comparable metabolic pathways for NMDs.

ENU-3 is a novel outgrowth and guidance protein in c. elegans

During the development of the nervous system, the migration of many cells and axons is guided by extracellular molecules. These molecules bind to receptors at the tips of the growth cones of migrating axons and trigger intracellular signalling to steer the axons along the correct trajectories. Previous work has identified a novel mutant, enu-3 (enhancer of Unc), that enhances the motor neuron axon outgrowth defects observed in strains of Caenorhabditis elegans that lack either the UNC-5 receptor or its ligand UNC-6/Netrin, enu-3 single mutants have weak motor neuron axon migration defects. Both outgrowth defects of double mutants and axon migration defects of enu-3 mutants were rescued by expression of the H04D03.1 gene product. Enu-3/H04D03.1 encodes a novel predicted putative trans-membrane protein of 204 amino acids. ENU-3 is expressed weakly expressed in many cell bodies along the ventral cord, including those of the DA and DB motor neurons.

ENU-3 is a novel outgrowth and guidance protein in c. elegans

During the development of the nervous system, the migration of many cells and axons is guided by extracellular molecules. These molecules bind to receptors at the tips of the growth cones of migrating axons and trigger intracellular signalling to steer the axons along the correct trajectories. Previous work has identified a novel mutant, enu-3 (enhancer of Unc), that enhances the motor neuron axon outgrowth defects observed in strains of Caenorhabditis elegans that lack either the UNC-5 receptor or its ligand UNC-6/Netrin, enu-3 single mutants have weak motor neuron axon migration defects. Both outgrowth defects of double mutants and axon migration defects of enu-3 mutants were rescued by expression of the H04D03.1 gene product. Enu-3/H04D03.1 encodes a novel predicted putative trans-membrane protein of 204 amino acids. ENU-3 is expressed weakly expressed in many cell bodies along the ventral cord, including those of the DA and DB motor neurons.