Did RNA droplets help originate life on Earth? UB researcher awarded Hypothesis Fund to explore

BUFFALO, N.Y. — The RNA world theory suggests that life on Earth began with RNA molecules that copied themselves. It’s believed this self-replication eventually gave rise over millions of years to DNA and protein, which then formed with RNA to create cells. 

Yet RNA would seem ill-suited to serve such an important role in the harsh environment of the prebiotic world — it’s known to destabilize under high temperature and pressure.

Priya R. Banerjee, PhD, associate professor of physics at the University at Buffalo, believes the key to solving this puzzle may be RNA’s intrinsic ability to form liquid-like droplets at high temperatures, which may have protected it from harsh conditions and compartmentalized its functions.

Banerjee has now received a seed grant from the Hypothesis Fund to better study these RNA droplets and their potential role in the origin of life on Earth. 

The project, “Liquid RNA Condensates as Programmable Scaffolds for Compartmentalization and Catalysis,” was selected for the boldness of the science, as well as Banerjee’s willingness to take risks and go after a big idea, according to the Hypothesis Fund, which announced the award this week. 

Hypothesis Fund seed grants fund innovation research at its earliest stages, typically before there is any preliminary data, with the goal of supporting high-risk, high-reward ideas that may not be funded or pursued otherwise. 

“Dr. Banerjee’s project brings unique insights into the origin of life by understanding the biophysical properties and self-organization principles encoded into RNA molecules. His hypothesis is bold and innovative and has the potential to answer conundrums in how life may have arisen with RNA, while also bringing insight to the development of more effective RNA-based interventions,” says Hypothesis Fund Scout Taekjip Ha, PhD, professor of pediatrics at Harvard Medical School and Cellular & Molecular Medicine at Boston Children’s Hospital. 

According to RNA world theory, RNA served functions in the primordial soup later done by DNA and protein — encoding genetic material and catalyzing chemical reactions. 

However, the theory is hotly debated. Key objections include thermal instability of RNAs and a lack of mechanistic understanding of how RNA-driven compartmentalization was achieved in the prebiotic world. 

Banerjee, who is also director of graduate studies in the UB Department of Physics, has recently reported an unexpected discovery of RNA phase separation into droplets, or condensates, when exposed to high temperatures. He is now studying how these droplets, which are also formed by DNA and protein, impact cellular function and disease processes. 

“We posit that temperature-controlled reversible and dynamic droplet formation by RNA molecules can address this key knowledge gap,” Banerjee says. “Our working hypothesis is that tiny RNA liquid droplets are programmable microscale compartments for RNA biology.”

By shedding light on the molecular origin of RNAs’ thermo-responsive droplet formation, the project could determine the role of the droplet state of RNAs in diverse biological functions, Banerjee says. 

The project is expected to last for 18 months.