Researchers discover cellular interactions that play key role in gene silencing
Each eukaryotic cell has an enclosed nucleus that houses its genome. The barrier between the nucleus and the cytoplasm is the nuclear envelope. The nuclear envelope contains channels called nuclear pores, which allow the exchange of large molecules between the nucleus and the cytoplasm. Each Nuclear Pore Complex (NPC) is, as its name implies, a sophisticated molecular machine composed of dozens of proteins, many of which have functions not well understood. One of the NIH Common Fund Technology Centers for Networks and Pathways (National Center for Dynamic Interactome Research) was established to develop innovative and dramatically new approaches for the isolation and analysis of macromolecular complexes, including the dynamics of how they work. In a new study funded in part through the Common Fund, researchers at the National Center for Dynamic Interactome Research have discovered a protein, located within these nuclear complexes, that plays a major role in gene silencing, which surprisingly is not related to the major role of transport. The protein, Nup170p, plays a key role in interactions with DNA in the nucleus thereby regulating which genes are being turned “on” or “off” in the cell. While the studies were conducted in single celled yeast, the results have implications for the regulation of gene expression in higher eukaryotes, including humans. In this study, the examination of nuclear pore complex interactions with the genome has advanced our understanding of gene silencing mechanisms and also paved the way for future studies of this type of complex intracellular interaction.
Van de Vosse DW, Wan Y, Lapetina DL, Chen WM, Chiang JH, Aitchison JD, Wozniak RW. A role for the nucleoporin Nup170p in chromatin structure and gene silencing. Cell, 2013 Feb 28;152(5):969-83. PMID: 23452847.
Genomes, contained within chromosomes, encode the hereditary information inside each of our cells. The Human Genome Project, completed in 2003, was a large scale effort to decode the full DNA sequence from humans. While this was a milestone in modern technology, we have now come to understand that in addition to the sequence, the three-dimensional conformation of the genome plays a fundamental role in the expression of genes. A novel method to address genomic conformations has now been developed by a research team funded in part by the NIH Common Fund National Technology Center for Dynamic Interactome Research. The newly developed technology, tethered conformation capture (TCC), allows for comprehensive analysis of how chromosomes interact with each other. The research team was able to apply computational models that allowed for the raw TCC data to be translated so that three-dimensional genome structures could be viewed. This new technology paves the way for follow-up studies that will yield even higher resolution of human genomes as they exist in cells, allowing researchers to study the complex interactions of chromosomes in different human cells.
Kalhor R, Tjong H, Jayathilaka N, Alber F, Chen L. Genome architectures revealed by tethered chromosome conformation capture and population-based modeling. Nat Biotechnol. 2011 Dec 25. PMID: 22198700.
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Having nutrients move throughout the body is as important for plants as it is for animals. It has long been known that humans have a heart to pump blood, but exactly how plants move their nutrients, primarily sugar, from the leaves to the rest of their bodies has been unknown. A group led by Dr. Wolf Frommer of the Carnegie Institution, funded in part by the Common Fund’s Building Blocks, Biological Pathways and Networks program, has now identified specific proteins within the SWEET family that have a major contribution to the movement of sugar from leaves to other important areas of plants. Using both the model plant system Arabadopsis and the rice plant, the researchers were able to identify these important proteins and then confirm their utility by eliminating the function in laboratory plants.
The findings from this team have major implications for both plants and humans. Knowing how sugar is moved through the plants has great potential for increasing the amount of food that can come from the parts of the plants we eat. This could have substantial ramifications for feeding the growing world population. Another important aspect is that, like us, plants can get sick. Some of the infectious microbes that make plants sick “highjack” the plants ability to move sugar so that they can feed on and damage the plants. Therefore, these new insights on how plants transport sugar can also have great potential for preventing the sickness of plants that are important for humans. The proteins that move sugars throughout plants might even have similarity to the proteins that do this in animals. This could lead to a better understanding of human diseases such as obesity and diabetes.
Chen LQ, Qu XQ, Hou BH, Sosso D, Osorio S, Fernie AR, Frommer WB. Sucrose efflux mediated by SWEET proteins as a key step for phloem transport. Science, 2012 Jan 13; 335(6065):207-11. PMID: 22157085
Similar to humans, plants can be sickened by infection with bacteria and other pathogens, resulting in crop losses of over $500 billion every year. Dr. Wolf Frommer of the Carnegie Institution, funded in part by the Common Fund’s Metabolomics program, has identified how pathogens “hijack” plant cells to divert nutrients away from the plant for their own use. In the November 24th online edition of the journal Nature, Dr. Frommer and colleagues describe a new family of proteins, called SWEETs, which transport sugar out of the plant cell. Several different types of pathogens can cause increased production of SWEET proteins, thereby releasing more sugar from the plant cell to be consumed by the pathogen as food. Mutations in a rice SWEET protein confer resistance to bacterial blight, indicating that interfering with the action of SWEETs may provide a new method to block a broad range of pathogenic infections and reduce crop losses. Interestingly, SWEETs are present in animals as well, including mice and humans, and may play a role in sugar transport from liver and intestinal cells. A better understanding of SWEET proteins may have important implications for the health of plants and humans alike.