A new study published in the journal Nature Structural & Molecular Biology has revealed how the framework of DNA has predisposed it to be the primary carrier of life-giving genetic information and not its molecular cousin RNA.
Using a cutting edge imaging technique, the study researcher were able to see how DNA’s double helix is a more robust molecule that can contort into various shapes to buffer against possible chemical destruction. In comparison, when RNA is shaped into a double helix it becomes too stiff and falls apart.
“There is an amazing complexity built into these simple beautiful structures, whole new layers or dimensions that we have been blinded to because we didn’t have the tools to see them, until now,” study author Hashim M. Al-Hashimi, a professor of biochemistry at Duke University, said in a news release. The study is likely to “rewrite textbook coverage” on DNA and RNA.
When the first model of the DNA double helix was published in 1953 by the famed Watson and Crick, the paper described just how DNA base pairs would fit together. Yet other scientists struggled to offer proof of this. In 1959, a biochemist named Karst Hoogsteen captured an image of a base pair that had a somewhat bent geometry, with one base turned 180 degrees in relation to the other. Subsequently, both Watson-Crick and Hoogsteen base pairs have been viewed in pictures of DNA.
DNA can absorb chemical damage in a way RNA cannot (Credit: Huiqing Zhou, Duke University)
Studying the Double Helix
Five years ago, the team behind the new study revealed how base pairs continuously switch back and forth between Watson-Crick and the Hoogsteen styles in the DNA double helix. Al-Hashimi said Hoogsteen base pairs normally appear when DNA is ensnared by a protein or harmed by chemicals. The DNA returns to its simpler pairing when it is discharged from the protein or the damage is repaired.
“DNA seems to use these Hoogsteen base pairs to add another dimension to its structure, morphing into different shapes to achieve added functionality inside the cell,” Al-Hashimi said.
In the new study, researchers set out to determine if the same phenomenon was occurring with RNA. Using a state-of-the-art imaging method referred to as NMR relaxation dispersion, researchers examined double artificial helices — one made of DNA and one made of RNA. Using the NMR process, the team could follow the flipping of individual bases that constitute the spiraling steps, pairing up based on either Watson-Crick or Hoogsteen rules.
Prior analyses indicated that at any particular time, one percent of the bases in the DNA double helix were changing into Hoogsteen base pairs. But when the team checked out the equivalent RNA double helix, they discovered zero detectable movement; the base pairs were all frozen in the Watson-Crick configuration.
The scientists wondered if their simulation of RNA was an exception or anomaly, so they developed a wide range of RNA molecules and screened them under a wide range of conditions, but still none seemed to change. They were concerned the RNA might actually be developing Hoogsteen base pairs, but that they were taking place so swiftly that they weren’t capable of catch them in the act. The team added a chemical referred to as a methyl group to a particular spot on the bases to stop Watson-Crick base pairing, so the RNA would be held in the Hoogsteen configuration. They said they were shocked to see the two strands of RNA then came apart.
The team said RNA doesn’t form Hoogsteen base pairs because its double helical structure is more packed together than DNA’s. Consequently, RNA can’t change one base without hitting another or moving around atoms, which would rip the helix apart.
“For something as fundamental as the double helix, it is amazing that we are discovering these basic properties so late in the game,” Al-Hashimi said. “We need to continue to zoom in to obtain a deeper understanding regarding these basic molecules of life.”
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