RIBOZYMES
MINIMALIST RNA
Polymer containing only two nucleotides functions as catalyst
A catalytic RNA molecule that contains only two different subunits has been constructed by chemists at Scripps Research Institute. The molecule, composed only of the nucleotides uracil and 2,6-diaminopurine, catalyzes a key reaction related to the polymerization of RNA: the joining of two pieces of RNA through formation of a phosphodiester linkage [Nature, 490, 841 (2002)].
 |
JUST RIGHT Hydrogen bonding between uracil (left) and 2,6-diaminopurine (right) is a winning combination for two-component ribozyme. |
Postdoctoral fellow John S. Reader and chemistry and molecular biology professor Gerald F. Joyce produced the ribozyme. "We wanted to show Darwinian evolution at its minimalist form," Joyce says. "In principle, all you need as the basis of Darwinian evolution is an information-containing molecule, and the minimal basis for encoding information in a molecule is two components."
This study asks an important question, says Alexander Rich, professor of biology at Massachusetts Institute of Technology, "namely, can you make a ribozyme with only one base pair? The answer is a resounding yes. It's a good demonstration of the structural potential of ribozymes, which is very large."
Scientists have long recognized that a two-component system could theoretically carry the genetic information needed to sustain life. Forty years ago, Rich first speculated that the earliest life on Earth might have used a two-letter genetic code instead of the four-letter code used today. Later, others suggested that this early life might have been based on RNA. The new experiments put some chemical foundation under both of these ideas.
The system "proves that a two-letter enzyme can do the chemistry of RNA replication," Joyce says. Yet, he adds, "I have no idea whether life actually began with two letters or not. Just because it's possible doesn't mean it happened."
The constructed ribozyme performs the same chemistry that a polymerase uses to copy an RNA molecule, Joyce points out, but it does so much more slowly. The ribozyme accelerates the reaction about 36,000 times over the uncatalyzed rate; modern polymerases are four or five orders of magnitude faster. |