LIFE ON EARTH may have originated with DNA's cousin RNA, but how the modern world evolved from the RNA world is still mostly unknown. Now, in a new study published last week in the journal Nature, what researchers think are ancient relics from the primordial ooze still lurking in modern biology might serve as the missing links bridging modern life with the RNA world.
HERE'S THE BACKGROUND — Nowadays, the main building blocks of life are DNA, which can store genetic data, and proteins, which include enzymes that catalyze vital biological reactions. However, DNA requires proteins in order to form, and proteins need DNA to form, raising the chicken-and-egg question of how protein and DNA could have formed without each other.
To help solve this mystery, scientists have suggested that life may have first primarily depended on RNA. Compounds known as nucleobases — adenine (A), thymine (T), cytosine (C), and guanine (G) — come together to form DNA. In RNA, uracil (U) is used in place of thymine.
RNA can store genetic data like DNA, serve as enzymes like proteins, and help create both DNA and proteins. Researchers have speculated that DNA and proteins later replaced this RNA world because they are more efficient at their respective functions.
However, RNA molecules continue to serve a vital role in biology. For example, messenger RNA helps convey genetic data from DNA inside the cell nucleus to the rest of the cell. Transfer RNAs shuffle amino acids, the building blocks of proteins, to factories within the cell known as ribosomes. Ribosomal RNA helps ribosomes synthesize proteins based on information from messenger RNA.
But how the chemistry of life moved beyond the RNA world isn’t fully understood. Nowadays, although RNA in ribosomes helps manufacture proteins, it partners with complex proteins in order to do so. It was unclear how the RNA world might have begun synthesizing proteins before complex proteins existed to help manufacture proteins.
WHAT THE SCIENTISTS DID — In the new study, researchers examined molecules other than the A, U, C, and G used in RNA. These so-called "non-canonical RNA bases" find use in transfer and ribosomal RNA.
In RNA, bases are combined with sugar molecules to form compounds known as nucleosides. Nucleosides can be combined with phosphorus-loaded chemicals to produce molecules known as nucleotides. RNAs are made up of strings of nucleotides.
Non-canonical nucleosides — ones that use different bases or sugars normally found in RNA — nowadays "are needed for RNA to fold into the right three-dimensional structure," study senior author Thomas Carell, a biochemist at Ludwig Maximilians University in Munich, tells Inverse. "They also give RNA the stability that is required for its function."
Moreover, non-canonical RNA nucleosides help increase the accuracy of the system used to decode genetic information. "Without these nucleotides decoding genetic information, the whole process is far too error-prone," Carell notes.
Non-canonical nucleosides can have amino acids linked with them. Carell and his colleagues reasoned that such compounds might have provided a way for ancient RNA molecules to help synthesize proteins. They synthesized RNA strands incorporating such non-canonical nucleosides to see what chemical reactions might happen.
WHAT THEY FOUND — The scientists discovered that RNA strands that possessed non-canonical nucleosides could result in complex chimeras of RNA and strings of amino acids known as peptides. In modern biology, proteins are made of long peptides.
"For me, the most surprising discovery was seeing how easily amino acids attach to RNA," Carell says. "Peptides can grow on RNA basically magically without much help from outside."
The researchers suggest the RNA world not only consisted of the four canonical nucleosides, but also a plethora of other nucleosides as well. These non-canonical nucleosides helped the RNA world shift to an RNA-peptide world, one with increasingly longer and more complex molecules, resulting in a DNA-RNA-protein world. Eventually, the four canonical nucleosides evolved to help encode data, whereas the other non-canonical nucleosides helped provide structure and stability.
"A potential critique could be that this type of RNA-peptide conjugate that we are proposing are not found anymore in nature today," Carell says. Still, the scientists believe "the fact that amino-acid-containing nucleosides are still present in transfer RNA is sufficient proof that such structures may indeed have existed."
WHAT'S NEXT? — In the future, the scientists would like to find peptides that grow on RNA that can serve as the kind of enzymes that life needs to function properly. "Particularly important would be the discovery of peptides that can help RNA replicate or that provide more stability to the RNA molecule," Carell says.