Going against all we know: This protein doesn’t need DNA to build other proteins

Chuck Bednar for redOrbit.com – Your Universe Online

Crack open any science textbook and it’ll tell you that DNA instruction are required to produce proteins. But a University of Utah-led team of researchers have discovered evidence suggesting otherwise.

Published Thursday in the journal Science, their findings show that it’s possible for amino acids (the building blocks of proteins) to be assembled without blueprints from DNA and messenger RNA (mRNA).

“This surprising discovery reflects how incomplete our understanding of biology is,” explained first author Peter Shen, a postdoctoral fellow in biochemistry at the University of Utah. “Nature is capable of more than we realize.”

To help explain the enormity of this discovery, the researchers compare a cell to a well-run factory and ribosomes to machines on an assembly line that makes proteins. They link together amino acids in a sequence specified by the genetic code, and when something goes wrong, the ribosome halts the process so that a “quality control team” can arrive on the scene.

In order to clean up the mess, the ribosome is disassembled, the blueprint is discarded and the incomplete protein winds up being recycled, the study authors explained. However, the study revealed that one member of this so-called quality control team, a protein known as Rqc2, has a somewhat surprising role in the protein-recycling process.

Before the unfinished protein is recycled, Rqc2 prompts the ribosomes to repeatedly add two of the 20 known amino acids, alanine and threonine, in an unspecified order. Continuing with the factory illustration, they compare the process to an assembly line that continues building despite not having instructions by putting random components together.

“In this case, we have a protein playing a role normally filled by mRNA,” said Dr. Adam Frost, co-senior author of the study and an adjunct professor of biochemistry at the University of Utah. “I love this story because it blurs the lines of what we thought proteins could do.”

These unusual proteins, which have apparently random sequences of alanines and threonines tacked on, are like “a half-made car with extra horns and wheels tacked to one end,” the study authors explained. It looks odd, and probably does not work normally, but the researchers believe that the nonsensical sequence likely serve a specific purpose.

It could serve as a indicator that the unfinished protein needs to be destroyed, or it could be a test in order to determine whether or not the ribosome is functioning correctly. Evidence suggests that one or both of these processes could be faulty in those individuals suffering from Alzheimer’s disease, Amyotrophic lateral sclerosis (ALS), or Huntington’s disease, they said.

“There are many interesting implications of this work and none of them would have been possible if we didn’t follow our curiosity,” said co-senior author Dr. Onn Brandman of Stanford University. “The primary driver of discovery has been exploring what you see, and that’s what we did. There will never be a substitute for that.”

Dr. Frost, who admitted that the idea seemed “far-fetched,” said that they first considered the phenomenon after witnessing evidence of it with their own eyes. He and his colleagues tweaked a technique known as cryo-electron microscopy to flash freeze, and then visualize, the quality control machinery in action. By doing so, they “caught Rqc2 in the act.”

Validating their hypothesis required detailed biochemical analysis, but new RNA sequencing techniques revealed that the Rqc2/ribosome complex could indeed add amino acids to stalled proteins because it also bound tRNAs (structures that bring amino acids to the protein assembly line). The tRNAs in question only carry the amino acids alanine and threonine.

“Our job now is to determine when and where this process happens, and what happens when it fails,” Dr. Frost concluded. Scientists from the University of Utah, the University of California at San Francisco (UCSF) and the University of Texas at Austin were also involved in the study.

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