Visualizing RNA activity within the brain tissues of live mice for faster and more accurate discovery and development of novel drugs
June 29, 2015
Kyoto, Japan - A group led by Assistant Professor Dan Ohtan Wang from Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) in Japan successfully visualized RNA behavior and its response to drugs within the living tissue brain of live mice by labeling specific RNA molecules with fluorescent probes. Their study, published in Nucleic Acids Research, can potentiallylead to faster, and more accurate screening processes for the discovery and development of new drugs.
RNA is a molecule that plays a key role within a living organism, holding information as to when, where and how much protein must be allocated, which is also responsible for controlling the biological reactions within a living cell. RNAs behave uniquely and are distributed unequally in each cell, existing more in some areas of the cell than others depending on environmental factors and cell conditions. In some cases, these chemical changes can put the cell's health at risk due to RNA disruption. However, it is unclear as to how the distribution of RNA molecules is regulated in the cell, and what causes them to act abnormally.
By introducing a non-toxic, fluorescent probe within the brain of live mice, the team succeeded in visualizing targeted RNA in the cell nucleus. This fluorescent probe emits varying intensities of light depending on RNA concentration levels enabling the team to effectively quantitatively analyze RNA in the living body. The imaging technique, for the first time in the world, quantitatively conveyed that the RNA behavior in live tissue differed from that of a cultured cell when a drug was administered.
Wang hopes that this new imaging technique can help reveal "the natural state of RNA," that allows us to observe the emergence and disappearance of RNA clusters in many types of species, including those that cannot be genetically engineered. "Our next goal is to investigate differences of RNA activity in a live, single cell, what regulates RNA activity, and compare healthy tissue and unhealthy tissue to elucidate gene expression mechanisms and pathologies caused by abnormal RNA activity."
ECHO-liveFISH: in vivo RNA Labeling Reveals Dynamic Regulation of Nuclear RNA Foci in Living Tissues
Ikumi Oomoto1,2, Asuka Suzuki-Hirano3,4 Hiroki Umeshima1, Yong-Woon Han1, Hiroyuki Yanagisawa5, Peter Carlton1, Yoshie Harada1,2, Mineko Kengaku1,2, Akimitsu Okamoto5,6, Tomomi Shimogori3, and Dan Ohtan Wang1
Nucleic Acids Research | Published Online 22 June 2015
- Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501, Japan
- Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501, Japan
- Brain Science Institute, RIKEN, Hirosawa, Wako City, Saitama 351-0198, Japan
- JSPS Research fellow, Japan Society of Promotion of Science, 5-3-1 Kojimachi, Chiyoda-ku,Tokyo 102-0083, Japan
- Advanced Science Institute, RIKEN, Hirosawa, Wako City, Saitama 351-0198, Japan
- Research Center for Advanced Science and Technology, University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8904, Japan
- Nikkei Sangyo Shimbun "Kyoto University succeeds in visualising RNA activity in mice" (June 26, 2015 Page 13)