The nucleolus was first discovered in the early 1830s as a creator of cell protein but new research has found that this structure also controls cellular growth as well as health. Clifford Brangwynne and his colleagues from Princeton questioned how a honey-like liquid held the capability of developing stable compartmentalized layers.
They published a paper in Cell journal on May 19th showing that the RNA and proteins of the nucleoli impulsively assemble into three liquid layers. These drastically different layers are thanks to their very different surface tensions and viscosities. The process works a lot like water and oil, which remain separate yet live in the same space. The nucleolus builds sub-compartments allowing it to carry out function. These findings may be able to help treat disease.
Brangwynne and his colleagues have already proven that many other organelles are phase-separated liquid droplets of both RNA and protein, much like the nucleolus. The most recent findings display how organelles are able to build structures that are tailor made for their specific duties, without the help of membranes.
Investigations were completed on nucleoli thanks to experiments with purified nucleolar proteins and living frog eggs cells, roundworms and cultured cells and a bit of computer modeling. Frog eggs have nucleoli that do not typically come into contact with one another because of their elastin actin network. The eggs were incubated within a pharmacological drug to break down that actin in order to promote fusion. This allowed biophysical properties to be viewed for each particular nucleolar layer.
In the protein testing, droplets for nucleolar proteins known as FIB1 and NPM1 would not fuse. Since FIB1 has a higher surface tension, it was completely engulfed by NPM1, which is exactly what happens in living cells. According to Steve Michnick, a biophysical chemist at the University of Montreal, the research establishes that the sub-organization of the nucleolus is created by one phase-separated body consuming another and also explains the physical properties that allow the change.
When it comes to the nucleolus, young RNA molecules move from the core of the organelle to the middle and outer components. As they move, they are modified. Nucleoli send out bits of RNA which go into the cytoplasm of the cell and link together to build ribosomes. Ribosomes produce thousands of proteins for every single cell.
Recent data shows that the nucleolus also coordinates cellular growth, regulating cell division and sets a timeframe for a cell to self-destruct. This means the nucleolus plays a major role in disease throughout the body. In cancer, for example, nucleoli produce proteins at a much higher rate than they are meant to, leading to over-division. Oncologists can view nucleoli in order to predict the spread of cancer based on its shape.
Researchers plan to continue the study of the nucleoli. The hope is to be able to create drugs that will target the organelle and look deeper into the nucleolar core-shell structure in order to diagnose and treat diseases quicker. P-bodies and Cajal bodies, for example, are not discussed often but appear to play very major roles in diseases such as Alzheimer’s and even amyotrophic lateral sclerosis. These organelles are also suggested to have a major effect on cell physiology.
Brangwynne says the research is very exciting and is amazed how complex structures such as the nucleolus are able to self-organize with their seemingly simple properties. He hopes the same simplicity will apply to how the organization may go awry during disease.