Discovery reveals how a gene-suppressing enzyme recognises genes’ product
Dr Chen Davidovich from the Monash BDI co-led an international team of scientists to shed new light on how genes are regulated. Dysregulation of gene expression leads to various diseases, including cancer. It is therefore critical to understand how genes are regulated, a process that is assisted by epigenetic modifiers: enzymes that introduce specific chemical changes to proteins and nucleic acids in the immediate vicinity of genes. The epigenetic modifier PRC2 is well-known for its role in gene repression, but what was not known - until now - was how it recognises gene’s product: RNA molecules. The team’s findings were published in Molecular Cell.
Researchers from Monash University’s Biomedicine Discovery Institute (BDI), in collaboration with an international team of scientists, have shed new light on how genes are regulated.
Genes in the human genome are made of DNA. Upon gene expression, a segment of DNA is copied into another molecule called RNA. How genes – and their RNA product – are regulated has been the focus of ongoing research by many scientists. When gene regulation goes wrong, diseases like cancer can occur. Therefore, knowing how enzymes — highly efficient protein nanomachines — work to switch genes on and off enables the development of new drugs and diagnostics.
One of these enzymes, formed by several proteins and called the Polycomb Repressive Complex 2 (PRC2), is essential to prevent thousands of inactive genes from switching on. By doing so, PRC2 regulates genes within a healthy human cell. Problems with PRC2 expression and function can lead to cancer formation or progression. Accordingly, there has been a large effort to understand how PRC2 works and how we can target it in order to treat cancer. It has been long known that PRC2 can bind to RNA that emerges from active genes, but it was not known how PRC2 recognises these RNA molecules.
The international research team, led by Dr Chen Davidovich from Monash University and Nobel Laureate Thomas Cech from Howard Hughes Medical Institute and the University of Colorado at Boulder, in collaboration with Monash Bioinformatics Platform, found that PRC2 interacts and binds to specific sites of RNA. Additionally, the researchers demonstrated that PRC2-RNA interactions can be blocked in the test tube using specific inhibitors that bind to RNAs that are normally recognised by PRC2.
The team’s findings were published today in the prestigious journal, Molecular Cell.
Dr Davidovich, an EMBL-Australia Group Leader from the BDI at Monash University and the ARC Centre of Excellence in Advanced Molecular Imaging explained how these findings could lead to new cancer treatments.
“These findings open new doors to develop strategies to target the RNA-binding activity of PRC2. More work does need to be done to translate this potential into therapeutics and to identify the circumstances where such inhibitors should be used,” Dr Davidovich said.
About the Monash Biomedicine Discovery Institute
Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.
About the Australian Research Council Centre of Excellence in Advanced Molecular Imaging
The $39 million ARC-funded Imaging CoE develops and uses innovative imaging technologies to visualise the molecular interactions that underpin the immune system. Featuring an internationally renowned team of lead scientists across five major Australian Universities and academic and commercial partners globally, the Centre uses a truly multi scale and programmatic approach to imaging to deliver maximum impact. The Imaging CoE is headquartered at Monash University with four collaborating organisations – La Trobe University, the University of Melbourne, University of New South Wales and the University of Queensland.
About EMBL Australia
EMBL Australia is a life science network that maximises the benefits of Australia’s associate membership of The European Molecular Biology Laboratory (EMBL). Officially launched in 2010, EMBL Australia aims to strengthen the nation’s global position in life sciences by creating opportunities for internationalising Australian research through the EMBL Australia Partner Laboratory Network, training the best students and early-career researchers and accessing key international infrastructure.