Self-Correcting Messeges
Robert D. Kornberg’s work may also provide support for theories on the origin of life. The fidelity of transcription refers to how accurate an mRNA transcript can be created complementary to the DNA template. Accurate transcripts are essential for proper protein synthesis and cell survival. Therefore, a unique transcription correction mechanism is thought to have evolved in RNAP to ensure such accuracy. Because RNAP’s active site alone is too weak for such mechanisms, it has been suggested that the transcript itself catalyzes the cleavage of a misincorporated base pairs (13).
Unlike in vitro studies, in vivo studies have shown that this transcript self-correction occurs in the absence of cleavage factors. Such factors normally help RNAP correct its messages at its active site. Two synthetic DNA-RNA hybrid helices were created; one containing an mRNA strand without errors and the other containing an mRNA strand with a non-complementary base pair at the terminal 3’ end. Both synthetic helices were then subjected to a magnesium-free RNAP. With the addition of magnesium ions, only the erroneous mRNA showed signs of cleavage whereas the error-free mRNA did not. Additionally, these studies show that RNAP backtracks or moves backwards on the mRNA and when this occurs, it is the terminal noncomplementary base pair that stimulates its own cleavage.
At the active center two magnesium ions participate in both mRNA synthesis and cleavage for error correction. However, unlike the first magnesium ion, the second magnesium ion (mg2+2) binds weakly to RNAP under normal conditions. Instead, this ion can be stabilized by the terminal noncomplementary base pair during RNAP backtracking. It is thought that during the correction mechanism, this terminal base pair causes mg2+2 to activiate a water molecule, which then serves to attack and cleave the erroneous base pair.
It should be noted that cleavage factors can also stimulate such cleavage of erroneous base paired nucleotides. However, these factors may be required only when RNAP has backtracked too far, which places the terminal base pair out of range for the cleavage reaction. Self-correcting mRNA transcripts are a unique discovery. Such self-sufficiency may even provide missing links to theories that DNA once evolved from an RNA world.