Israeli scientists have made a new breakthrough in the study of tiny, resilient organisms called hyperthermophiles — which have learned to survive in some of the earth’s hottest places, such as volcanic craters and underwater hot springs — by developing the first comprehensive, large-scale method to examine the organisms.
Researchers at the Weizmann Institute of Science show in a new peer-reviewed study that, contrary to popular scientific belief, the hyperthermophiles — whose name derives from the Latin for “lovers of extreme heat” — can modify their own RNA molecules at the core of their ribosomes, where cells manufacture protein, to adapt to extreme heat and survive.
“The hyperthermophile completely changes its chemical composition depending on different environments,” said Prof. Schraga Schwartz of Weizmann’s Molecular Genetics Department, speaking to The Times of Israel.
The research, led by Dr. Miguel A. Garcia-Campos, “goes a bit against the notion that fundamental processes inside the ribosome are fixed,” Schwartz said.
Participating in the study, which recently appeared in the prestigious journal Cell, were researchers from the National Cancer Institute, Jagiellonian University in Poland, and Tokyo Metropolitan University.
The findings may enable further development of RNA-based medical and industrial technologies.
A document of molecular biology
The ribosome is one of the earliest and most basic biological structures. It is transcribed into RNA, Schwartz explained.
“It’s the basic document of molecular biology,” he said. “Plants, humans, butterflies, bacteria — every single one of us has a full code for the RNA to build the proteins needed to allow them to maintain themselves and to design and proliferate.”
In the 1950s, scientists discovered that ribosomal RNA, or rRNA, undergoes “chemical editing,” meaning small modifications are added after the RNA is made. These changes, however, were hard to measure, so researchers could not gauge how much they varied between species or whether they changed when the environment changed.
“For many years, it was widely assumed, mainly based on research in yeast and humans, that RNA modification in the ribosome was uniform among all members of a given species and did not change with the environment,” Schwartz said.
But further evidence hinted that in some organisms, modification might be dynamic — shifting as needed to help the ribosome adapt. Schwartz said that proving this was difficult and time-consuming because there are many types of modifications, and older methods could examine only one type at a time.
Focusing on organisms that live in harsh environments
Schwartz’s team focused on extremophiles, organisms that love extreme environments.
They were interested in hyperthermophiles, tiny organisms that grow best in temperatures from about 60°C (140°F) to 100°C (212°F).
Schwartz’s team developed a breakthrough method that can detect 16 types of RNA modifications across dozens of samples at once.
The technique allowed the scientists to map RNA modification patterns in 10 single-celled organisms and compare them to four studies the researchers had done in the past.
The researchers tested whether these organisms could change their rRNA during their own lifetimes by growing the species at different temperatures.
They saw that as temperatures rose, the hyperthermophiles changed and adapted.
“We found hundreds of changes in hyperthermophilic species,” Schwartz said. In fact, the hotter the organism’s natural environment, the more modifications it performs, he said. This suggested that these organisms use extensive chemical editing to protect their ribosomes from heat damage.
Prof. Shulamit Michaeli, the VP for research and director of the Dangoor Center for Personalized Medicine at Bar-Ilan University, who was not involved with the study, told The Times of Israel that rRNA’s chemical modification “enables protein synthesis in an extremely hot environment, promoting thermophilic growth.”
She said the study “nicely demonstrates” the major impact of rRNA modification on the ability of cells to adapt to environmental stress.
This means that lessons can be learned from “the RNA-editing process that has undergone billions of years of refinement,” Schwartz said.
“There are many RNA-based technologies on the market or in development — from vaccines against pandemics and cancer diagnostics and therapies to gene-editing tools used in biotechnology and medicine,” he noted.
For example, since hyperthermophiles do well at high temperatures, they are used in many industrial processes, such as laundry detergents to clean clothes in hot water, or in molecular biology for DNA testing.
“Uncovering RNA’s secrets could pave the way for more reliable and efficient RNA-based technologies,” Schwartz said.
Asked about whether the June Iranian ballistic missile attack damaged his lab, Schwartz said, “Luckily, we didn’t get a direct hit.”
However, he said, “I can see the building that was directly hit from the window of my office. Somehow, the way we’re positioned, we got away with relatively mild damage.”
People around the world “have always been extremely supportive of us,” he added.
“Life is so diverse,” he said, returning to his research subject. “And yet, you have a single language, which is basically the RNA, and that’s what drew me to science in the first place. It was the realization that there’s this common, universal language among all species.”