A recent study has identified new biological ingredients that may help scientists turn genes on and off in order to control processes contributing to disease.
A collaboration between Xantha Karp, Central Michigan University biologist and faculty member, and the lab of John Kim, faculty member at Johns Hopkins University, analyzes how the processes that regulate gene expression are controlled.
“We have learned one more secret about the tiny mechanisms and processes in our bodies that are flipping the switches as our cells develop,” Karp said. “Regulation of our genes is a major difference between humans and other living things, such as the worms used in this study.”
The regulation of genes—how, when and to what extent they are expressed—is what sets humans apart from other living things. Similar to a factory assembly line, gene expression is a process with many phases. The initial instruction manual, DNA, is kept in the nucleus of every single cell in our bodies. When the manual is sent down to the factory floor through a process called transcription, it does so in the form of a molecule called messenger RNA.
In a typical process, messenger RNA continues moving along the line until it undergoes translation and produces a protein. Proteins control the behavior of cells, helping them divide or preventing them from dividing, for example. Translation into a protein is a tricky process, however. If certain proteins are missing or present in the wrong amounts, this can lead to diseases such as cancer.
“Translation is similar to the final step in the assembly line,” Eric Montoye, CMU graduate assistant and co-author, said. “Proteins should be the final product created in the factory, but scientists have recently found the translation process can be interrupted.”
The interrupters are called microRNA, tiny RNA molecules that are an essential part of gene regulation. MicroRNAs stop specific messenger RNAs from being made into proteins, but they cannot do this alone. MicroRNAs work together with a group of proteins to form the microRNA-induced silencing complex, a team that can block the translation process.
MicroRNA, though a fairly new piece of the biological puzzle, is very important. Some microRNAs help stem cells develop, and others help cells protect themselves against cancer.
However, the microRNA-induced silencing complex group needs a specific chemical change in order to do its job appropriately.
“When the chemical change doesn’t happen, translation is not shut down and some proteins are overproduced,” Karp said. “This causes cells to make the wrong choices during development and can make living things very sick.”
Karp’s research on microRNA focuses on the specific changes these tiny pieces make when the worms she studies enter into a hibernation period called dauer. It appears that the hibernation phase can somehow boost microRNA activity which can help cells that previously developed incorrectly develop without issue. Her future research will look into how specific cells regulate their genes when in the dauer phase, hoping to determine which on switch can help stem cells stay healthy over long periods.
The study appears in the Proceedings of the National Academy of Sciences. It was supported by the American Cancer Society, the National Institutes of Health and the National Center for Research Resources. Additional collaborators on the study were Amelia Alessi, Vishal Khivansara, Ting Han and Mallory Freeberg, from the University of Michigan, and Patricia Tu and John Yates III, from Scripps Research Institute.