Before the DNA World: Life with an Extra OH
Story posted April 04, 2003
Nobel Laureate Thomas Cech spent two days at Bowdoin recently teaching classes and meeting with students. At Common Hour, Cech talked about his years of scientific exploration and why he finds RNA fascinating, even though DNA gets all the press. Common Hour was the second of two lectures he gave.
His talk was titled "Before the DNA World: Life with an Extra OH." The extra OH (hydroxyl) in its structure is one of the characteristics that distinguishes RNA from DNA.
While DNA has gained prominences in the media and in the popular imagination, Cech finds RNA to be more interesting. He told the audience about the discovery he and his colleagues made twenty years ago that led him to this fascination with RNA.
"You all known the central dogma...that DNA makes RNA makes protein," he said. DNA contains the genetic codes of an organism, but not all genetic codes required for "life" are DNA. Viruses, for example, don't even have DNA; RNA does all of the communicating and replicating.
"So clearly, RNA can be a reputable carrier of information," he said.
What Cech and his colleagues discovered, however, is that RNA also has the ability to speed up chemical reactions, just as a protein would, something DNA is unable to do.
"How can RNA have this extra capability that we don't find in the double helix of DNA?" he asked.
The important difference that gives RNA this ability is that it's a single strand. Instead of DNA's famed double helix, made up of two strands bound together, RNA is a single strand, which allows it to fold and bind to itself to form new structures and shapes.
"And shape is the key to being able to act as a biological catalyst," Cech said.
Cech was quick to point out that it made sense for DNA to be made up of this less flexible, but more stable double strand.
"You don't want the storehouse of your genetic information to be going off rearranging itself and doing chemistry," he said.
In about 1980, Cech began working with a simple organism called tetrahymena thermophila. In the gene that he and his collaborators were studying, they noticed that coded sequences, known as exons, were interrupted by noncoding sequences, known as introns, something now known to be a common occurrence.
"In fact, a typical human gene might have a dozen of these intron interruptions," Cech said. In some cases, the total length of the intron interruptions is even longer than the coded portion, though scientists are still not sure why introns exist. When the information is copied to make a precursor RNA, the intron is copied right along with the proper code.
"You can think of it like a video tape with a large commercial message in the middle of your favorite movie," Cech said.
Before the final form of the RNA is produced, the intron portion is cut out of the RNA code, as though someone took scissors to it at both ends. Cech and his colleagues wanted to investigate this process, and to their delight, they were able to observe this splicing within a test tube, "the first step toward figuring out the machinery responsible," Cech said. "It's very unusual in science for an experiment to work the first time, so we were very surprised by this."
The scientists were also surprised because the splicing occurred with or without the presence of protein enzymes. They had assumed that the protein enzymes would be the "machinery responsible," since protein enzymes are the catalysts for most reactions. Their belief that protein enzymes were involved in the splicing was so firm that they assumed some protein was sticking to the RNA.
So they boiled the sample. But still the splicing occurred.
So they added detergent. Again, they still had splicing.
So they boiled the sample along with the detergent. Splicing again.
Finally, in 1982, they created the precursor RNA artificially, ensuring that there was no way protein enzymes could have affected the sample. And splicing still occurred.
At last the scientist were ready to believe: "The RNA was really splicing itself, and there was no protein enzyme that as responsible," Cech said.
The single strand nature of the RNA enabled it to fold over on itself, forming new structures that allowed it to catalyzed the splicing. Some of these new structures even resemble the structure of proteins.
Now, 20 years after the discovery of the splicing in the RNA of the tetrahymena thermophila, scientists know of 1,500 self-splicing RNAs. Since the ability to reproduce is one of the characteristics that is common to all "life" forms, some have even speculated that this ability of RNA to act as a catalyst might be a clue to how the first self-replicating organism developed and the world moved from" primordial soup" to the repository of the many life forms to be found today.
Of course, we may never know for sure.
"When you're talking about the origin of life on earth, you're talking about a historical question, not a scientific question," Cech said. "If somebody doesn't believe it, you can't prove it, you can only prove that it was possible."
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