In recent years, it has become clear that the genetic code is far more complex than previously assumed. In addition to the well-known building blocks adenine, cytosine, guanine, and thymine, numerous chemical variations play an important role. Scientists now assume that the newly discovered nucleic acid modifications may form a second layer of information that extends and complements the genetic code. "The new discoveries are rather like umlauts that extend the standard alphabet," explained Professor Mark Helm of the Institute of Pharmaceutical Sciences and Biochemistry - Therapeutic Life Sciences at Johannes Gutenberg University Mainz (JGU). Helm is the coordinator of the priority program "Chemical Biology of Native Nucleic Acid Modifications", which the German Research Foundation (DFG) has now agreed to fund.
This nationwide priority program will start in 2015 and, according to plans, will continue to receive DFG support for six years. "We are lucky enough in Germany to have some of the leading international researchers in all the core areas in this field and we thus intend to explore this subject with the help of a country-wide network," said Helm. Decoding the information in the modified DNA and RNA bases and nucleosides is a hot topic in chemical biology right now.
Before 2009, scientists were convinced that only the four Watson-Crick bases plus a fifth base called 5-methylcytosine code for the genetic information that is key to life. Then three additional DNA modifications were uncovered in quick succession, which are postulated to act as switches that regulate gene functions. The switch can be used to activate or deactivate a gene. "We are looking at a completely new coding mechanism that had previously escaped our attention," Helm pointed out. On the other hand, scientists have long known that RNA, which is responsible for translating the genetic code into proteins, contains more than 150 different modified nucleosides. The purpose of these, however, is still largely unknown.
The new research network will closely examine the molecular details of the modifications in naturally occurring nucleic acids. This will involve, among other things, detecting and identifying modifications, localizing and quantifying them, and uncovering both their structure and function. In an initial period, an emphasis will be on methods from chemistry and structural biology, allowing to connect to scientists from the life sciences in joint projects. The German Research Foundation will issue a call for proposals in this innovative and interdisciplinary research program.