Beyond DNA and Histones: Chuan He’s Exploration of RNA Modifications and Gene Expression
Winner Interview 2023: Life Sciences
Dive into the world of Chuan He's pioneering research on RNA modifications, unraveling a hidden layer of biological regulation beyond the central dogma in life science. Explore how these modifications impact gene expression, from DNA to RNA to protein. Discover the profound implications for mammalian and plant development, human diseases, and the conservation. Join the journey of innovation, where basic discoveries pave the way for biotech therapies and sustainable agriculture solutions.
Which wall does your research break?
In the central dogma of life science, DNA encodes genetic information. That information is passed on to RNA, and then to protein. Protein executes most biological functions. However, RNA is not merely a passenger of information. It too has fundamental roles in affecting gene expression or genetic information flow in the central dogma, from DNA to RNA to protein. For instance, microRNAs are a group of short RNAs that significantly impact protein translation from messenger RNA. What I work on is another major mechanism: RNA chemical modifications. We have shown that some of these RNA modifications not only affect protein translation from mRNA but also regulate transcription, or the synthesis of mRNA from the DNA templates. So we study RNA modifications that affect both translation (the RNA to protein step) and transcription (the DNA to RNA step) in the central dogma. After we uncovered this new layer of biological regulation, it became clear that this mode of regulation broadly influences mammalian and plant development and impacts a wide range of human diseases. Biotech companies have been set up to develop new therapies based on basic discoveries, and we have been working on promoting plant growth and increasing crop yield and their tolerance to climate change using technologies developed from our research.
What inspired or motivated you to work on your current research or project?
Our genome has about 3 billion base pairs, but each of us has tens of trillions of cells. Obviously, the genomic DNA sequence is not enough to encode all the complexity of us. Chemical modifications on DNA and protein add additional layers of complexity. In 2008, we started to ask the question of whether RNA modification could also be used to broadly regulate gene expression. We made the first discovery in 2011, and since then I am excited that modifications on RNA that we work on are some of the most fundamental mechanisms to impact almost all life processes. I am particularly motivated by our recent plant biology work that shows we can modulate RNA methylation to dramatically promote crop yield and their resilience to drought and higher temperatures (climate change).
In what ways does society benefit from your research?
We and others are starting to realize that misregulations caused by aberrant RNA modification lead to various human diseases. These are targets for future therapies. I am particularly intrigued by the potential impact of our plant biology work done in collaboration with my former postdoc, Guifang Jia. We showed that modulation of RNA methylation in plants (rice and potato, but also other crops) can increase yields by ~50% in the field. These plants have much more extensively developed root systems, which allow them to better withstand drought and other stresses. These are plants that may better cope with challenges from climate change and offer a potential path to help address the issue of food security.
Looking ahead, what are your hopes or aspirations for the future based on your research or project?
There are two goals. The first is to learn new knowledge. For example, we know the type of RNA methylation we work on is critical to almost all stem cell differentiation and development. We want to understand how that works—how RNA methylation modulates various stem cell differentiation or enables a fertilized egg to eventually develop into an animal or a human. When there are defects in these programs, or when they should be turned off but remain active after development, human diseases can arise. The second goal is to have a social impact. Understanding the basic pathways and mechanisms allows for the development of new therapies. We also take what we learn from animals and apply it to engineer next-generation plants.
