New chemical substances present in all life on earth

The multitude of molecules that make up living things I so complex that biologists have been ignoring an entire class of them—until now. This lack of biochemistry is neither uncommon nor difficult to find; it's just that no one has thought to look for it before. s

"This is an amazing discovery, the discovery of a whole new class of biomolecules," said Stanford University biochemist Caroline Bertozzi, "and it was a bombshell because it showed that cells have Biomolecular pathways that are completely unknown to us."

Biologists have a fairly good understanding of our major molecular structures. You have carbohydrates (like starch), lipids (fat), nucleic acids (DNA), and proteins (muscle).

These are further divided into subtypes; for example, cellulose and sugars are carbohydrates. Then there are combinations between these groups, such as different sugars that combine with lipids in red blood cells to form the A, B, AB, and AAAA blood groups.

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Glycans are chains of sugar molecules that can bind to fats and proteins through the process of glycosylation, helping them transport through cells or fold into the correct shape. They are involved in many fundamental processes of biology, from embryonic development to pathogen recognition.

The researchers, led by biochemist Ryan Flynn, now at Boston Children's Hospital, found that glycans can also attach to noncoding RNAs.

This is a surprising phenomenon because RNA was previously thought to function only inside cells—in the nucleus and body fluids—while glycans are typically separated from cells by small cellular organelles or membranes on the cell surface.

"If you believe the textbooks, RNA, and glycans exist in two different worlds," Bertozzi said.

They solved this problem by labeling ethylene glycol molecules with sialic acid in laboratory cells and extracting the RNA. As expected, some purified RNAs had a sialic acid-tagged sugar coating.

The team then found glycogen RNA in every cell they examined—in humans, mice, hamsters, and zebrafish—species separated by evolution over hundreds of millions of years. This suggests that these molecules may have some important biological function that has been preserved in life on Earth.

Flynn and colleagues compared RNA fragments of glycogen RNAs to RNA databases and also found that some of these molecules matched disease-associated RNAs.

"Some RNAs that are modified by glycans to form sugar RNAs have a dirty history of association with autoimmune diseases," explained Bertozzi.

It was previously thought that these RNA fragments were virtually inaccessible to our immune system because they were safely tucked inside our cells and only released when the cells died.

"We found that sugar RNAs, like proteins and lipids, are present on the cell surface," Flynn told Nancy Flisler of Boston Children's Hospital. "This is exciting because it means that glycoRNAs can b Involved in cell-to-cell communication. This was previously considered a no-go zone for RNA, which does not function on the cell surface." e e e e e directly

We think about this a lot now, but you can imagine scenarios where glycoRNAs might act in parallel with other cell surface biomolecules such as glycoproteins/lipids, but with different kinetics, stability, or conformations.

The ability of glycans to attach directly to RNA seemed unlikely, so the team suspected that there was also a third, very small molecule that acts as the glue.

They point out that not all glycans contain sialic acid -- which they use to detect glycoribonucleic acid -- so they may have missed more species found in this molecular class.

"You ask a lot of questions when you discover something as completely new as these RNAs," Flynn said. While the function of glycoRNAs remains a mystery, their discovery promises to soon lead to more answers, possibly related to Some people h trouble with their immune system. having

The research was published in the journal Cell.