Living things/Medicine

Tetsuro Hirose

Finding New Genetic Programs by the Dark Matter of the Genome

Tetsuro Hirose , Professor

Institute for Genetic Medicine/Graduate School of Medicine

High school : Higashi Katsushika High School (Chiba)

Academic background : Nagoya University Graduate School of Science

Research areas
Molecular Biology, Cellular biology, RNA biology
Research keywords
RNA, Genome Science, Cellular Biology, Disease-related Protein, Neurodegenerative Disease

What sort of research are you conducting?

The human genome is a DNA molecule made up of four types of nucleotides linked together in a chain of 6 billion. Inside are all the biological programs to develop the human body and everything needed for it to survive. Biological programs are the production of the right proteins in the right places. Therefore, until now, in molecular biology, the process where information in DNA was copied by RNA and then translated into protein was the focus of research. However, here's where things get interesting. The area that codes the protein information in the human genome makes up only 2% of the whole. So what is the remaining 98% for? Until recently, the remaining area was thought to be a meaningless "junk area," and why there was such a large meaningless area remained a mystery.

Figure 1  At the beginning of this century, it was discovered that the junk area that made up much of the human genome produced the unknown ncRNA and was called "the dark matter of the genome."

However, upon entering the 21st century, it was discovered that these junk areas produced large amounts of non-coding RNA (ncRNA), and a new way of thinking- that these junk areas actually have a new previously unknown genome function that is carried by the ncRNA- was born (Figure 1). ncRNA is also known as "the dark matter of the genome." Discovering the function of this dark matter is an important issue for biology going forward. At my laboratory, we are working to discover the new function of ncRNA. In the 20th century biology, it was generally thought that the function of RNA was to act as the template for the translation to protein. However, with ncRNA, as the name implies, the RNA has its own distinct function without carrying protein coding information. We are trying to discover what kind of biological function ncRNA, the "dark matter of the genome," fulfills through what sort of mechanism.


What is your objective?

Aside from as an intermediary for protein coding, what sort of function can RNA serve? We have discovered an ncRNA that serves as the framework for a specific structural body inside the cell nucleus and is responsible for shaping that structure. This structure is called a paraspeckle, and is a massive ribonucleoprotein (RNP) made up of ncRNA and over 40 types of proteins. A paraspeckle, to draw a comparison, is an ultra-large RNP with a mass of over 1,000 times that of the commonly known ribosome (Figure 2). We have come to understand ncRNA acts as a sponge, absorbing and excreting various proteins within this structure. Among the proteins that come in and out, we've discovered numerous important proteins that are involved with neurological diseases and cancer. Even more interesting is that in a patient with neurodegenerative diseases, this structure is abnormally formed, indicating the possibility of a direct relationship between ncRNA and the outbreak of the disease. Therefore, ncRNA research may lead to discovering the mechanism behind the onset of such serious diseases and the development of therapeutics. We are looking to discover new biological phenomena and patient disease factors through understanding the yet to be known functions of ncRNA. And we hope to understand the working principles etched in the genome.

 Figure 2  The discovery of a non-coding RNA that serves as the framework of a nuclear body. The nuclear body (paraspeckle) is a massive conjugate made up of the ncRNA and numerous proteins, and appears as the white dots in the picture on the right. The blue area (DNA) is the cell nucleus.



What do you enjoy about your research?

The joy of discovering new phenomena not found in any textbook is something unparalleled. No doubt many researchers are people who have experienced that feeling at least once. As the name "the dark matter of the genome" implies, ncRNA research is a field that started after entering the 21st century and is mostly uncharted territory. It is an area where researchers are free to be pioneers. The chance to make new discoveries that would have been unthinkable with conventional biology may be closer than you think. We are awaiting young challengers.