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DNA owes its fame to the fact that it encodes the information corresponding to proteins, in the form of discrete pieces of information that we call genes. First of all, we should bear in mind that not all the information in the genome encodes proteins; there are long and long stretches of DNA which act as spacers between genes, or as targets for proteins which must bind specific regions promoting conformational changes that in turn promote or inhibit the expression of certain proteins. In a multidisciplinary work, including computational, stem cell and developmental biologists and recently published in Cell 1, one of these lncRNAs and its critical function is described. This molecular version of William Wallace turned out to be a chain of RNA formed by about 600 nucleotides, and they found no protein codified in its sequence.
This work by Mapping Ignorance is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0. Enzymes are protein catalysts that speed biochemical reactions by facilitating the molecular rearrangements that support cell function. Many of the molecular transformations that occur within cells require multiple steps to accomplish. Sometimes, the enzymes involved in a particular metabolic pathway are physically connected, allowing the products of one reaction to be efficiently channeled to the next enzyme in the pathway. Not only do cells need to balance catabolic and anabolic pathways, but they must also monitor the needs and surpluses of all their different metabolic pathways. Such up- and down-regulation of metabolic pathways is often a response to changes in concentrations of key metabolites in the cell. The five phases of mitosis and cell division tightly coordinate the movements of hundreds of proteins. Although mitosis and meiosis both involve cell division, they transmit genetic material in very different ways. Scientists were able to identify chromosomes under the microscope as early as the 19th century.
However, its role as the keeper of the critical information needed to construct an organism would be useless without the help of a very close relative, with a strikingly similar chemical composition but subtle, yet critical differences.
Klattenhoff and collaborators were interested in the analysis of this kind of molecules in the area of cardiogenesis.
The effect of Braveheart (the gene, not the film) depletion on the gene expression pattern of mouse embryonic stem cells. Stem cell populations mutate and expand responding to these changes in genetic profiles, losing on their way the capacity to produce different lineages and commiting themselves to a particular one.
Surely, it would be a piece of surprise for the warriors of ancient Scotland to know that their gestures form part of the discovery of cellular processes.
He has worked in signal transduction pathways regulated by protein phosphatases and involved in cell proliferation, glycogen metabolism and protein degradation.
Recall that chemical reactions convert substrates into products, often by attaching chemical groups to or breaking off chemical groups from the substrates. In fact, this binding and shape changing ability is how enzymes manage to increase reaction rates. An activator molecule (green pentagon) can bind to an enzyme (light green puzzle shape) and change its overall shape.

Recall, for instance, that cells split one glucose molecule into two pyruvate molecules by way of a ten-step process called glycolysis. At each step, the molecule is transformed into another form, due to the presence of a specific enzyme. For example, pyruvate dehydrogenase is a complex of three different enzymes that catalyze the path from pyruvate (the end product of glycolysis) to acetyl CoA (the first substrate in the citric acid cycle). They disassemble large molecules into simpler building blocks and then use those building blocks to create the new components they require. For example, if supplies of glucose start to wane, as might happen in the case of starvation, cells will synthesize glucose from other materials or start sending fatty acids into the citric acid cycle to generate ATP.
In this process, energy is either stored in energy molecules for later use, or released as heat. In order to bolster a particular pathway, cells can increase the amount of a necessary (rate-limiting) enzyme or use activators to convert that enzyme into an active conformation. For example, a cell may take stock of its levels of intermediate metabolites and tune the glycolytic pathway and the synthesis of glucose accordingly.
During mitosis, chromosomes attach to a spindle of microtubules that distribute them equally to two daughter cells. As a bonus, site members have access to a banner-ad-free version of the site, with print-friendly pages.Click here to learn more.
We are talking about ribonucleic acid or RNA, and in the present series of posts we will revise some quite novel and fascinating molecular processes controlled exclusively by the RNA version of some genes.
By using the technique of RNA interference, the researchers could study the effect of depleting Braveheart in ESCs: in doing so, they could learn not only in which way having or not Braveheart affected the cells, but also what other genes and the expression of which proteins was affected or not by its absence. The interesting finding here is how critical results the activity of this long, non translated RNA in determining that the cells in which it is present embrace the fate of becoming precursors of the cardiovascular system.
For example, in the final step of glycolysis, an enzyme called pyruvate kinase transfers a phosphate group from one substrate (phosphoenolpyruvate) to another substrate (ADP), thereby generating pyruvate and ATP as products (Figure 1). In many cases, enzymes function by bringing two substrates into close proximity and orienting them for easier electron transfer.
This coordinated series of chemical reactions is an example of a metabolic pathway in which the product of one reaction becomes the substrate for the next reaction.
Such a reaciton pathway can create a new molecule (biosynthesis), or it can break down a molecule (degradation).
Within this complex, intermediate products are passed directly from one enzyme to the next. The breaking down of complex organic molecules occurs via catabolic pathways and usually involves the release of energy. Conversely, in times of plenty, excess glucose is converted into storage forms, such as glycogen, starches, and fats. Anabolic pathways then build new molecules out of the products of catabolism, and these pathways typically use energy. Conversely, to slow down or halt a pathway, cells can decrease the amount of an enzyme or use inhibitors to make the enzyme inactive.

In some instances, the products of a metabolic pathway actually serve as inhibitors of their own synthesis, in a process known as feedback inhibition (Figure 5). After some years and with the quick acquisition of genomic knowledge, this central idea soon was replaced by a dynamic view of the molecular machinery of the cell, where nucleic acids and proteins interact constantly in order to perform cellular functions.
Summarizing, the conclusions are that Braveheart is not a gene required for the survival of the embryonic cells; but is critical to make them transform into cardiac cells.
And this is achieved by activating a critical switch, a protein called MESP1 that is able to activate a series of genes implicated in the development of all cell types in the heart. This transformation enables the enzyme to better bind with its substrate (light pink puzzle piece).
Consequently, the intermediate products of a metabolic pathway may be short-lived (Figure 3). Through catabolic pathways, polymers such as proteins, nucleic acids, and polysaccharides are reduced to their constituent parts: amino acids, nucleotides, and sugars, respectively. For example, the first intermediate in glycolysis, glucose-6-phosphate, inhibits the very enzyme that produces it, hexokinase. In this context, several other functions of RNA apart from its main role involving the transcriptional and translational processes, started to be described. For example, when inhibitor molecules bind to a site on an enzyme distinct from the substrate site, they can make the enzyme assume an inactive conformation, thereby preventing it from catalyzing a reaction. In contrast, the synthesis of new macromolecules occurs via anabolic pathways that require energy input (Figure 4). In the last decades these novel findings gave rise to a large family of different RNA types regarding their size and function in the cell. The one we want to focus on belongs to the class of long, non-coding RNA or briefly, lncRNA. Conversely, the binding of activator molecules can make an enzyme assume an active conformation, essentially turning it on (Figure 2). The effect of Braveheart, promoting the actions of MESP1, appears to function by an interaction mediated by other player called SUZ12. Particularly a very well known example is Xist, a non-translated RNA involved in the mechanism of silencing the expression of an entire X chromosome in female mammals. SUZ12 is a repressor, an enemy of Mesp1 and other genes that promote certain fates for a cell; when Braveheart attaches to SUZ12, impedes its repressive action and Mesp1 is free to start the revolution, making cells run towards a cardiac fate. This is a very interesting process that would deserve an entire article for itself, so let’s just keep the notion that a long chain of ribonucleic acid can be transcribed with the only mission of interacting with a particular molecular device, affecting its function. Braveheart tasks do not stop here, since it is also critical for the correct physiology of cardiac cells in more advanced stages of differentiation.

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