July 28, 2006 | David F. Coppedge

Self-Correcting RNA: Is It a Missing Link?

A team of Russian scientists at Rutgers discovered a remarkable phenomenon: RNA that proofreads itself during its own synthesis.  The work was reported in Science1: “We show that during transcription elongation, the hydrolytic reaction stimulated by misincorporated nucleotides proofreads most of the misincorporation events and thus serves as an intrinsic mechanism of transcription fidelity.”  It has already been known that DNA transcription and translation includes a whole suite of error-correcting mechanisms, but this is the first instance of RNA self-correction.
    The researchers did not comment on the evolution of this capability except to state that it “is likely evolutionarily conserved” (i.e., unevolved in all living organisms), and that in an RNA-protein world, a “proofreading and repair mechanism similar to the one described here could have allowed a large RNA genome of the last common universal ancestor to exist.”  This is because without an accurate proofreading mechanism even in an RNA world, duplication fidelity would have been too low for evolution: “the relatively low fidelity of RNAP-catalyzed synthesis could not have been sufficient for stable maintenance of large RNA genomes in the absence of cleavage factors.”
    Patrick Cramer (Gene Center Munich), however, writing in the same issue of Science,2 launched their final, speculative paragraph into a story of how this RNA must be a missing link.  Starting with the admission that “Precision can be vital,” Cramer immediately invoked the E word: “cells have evolved processes for proofreading and correction to shut down the propagation of errors” in the DNA-to-protein pathway.  Referring to the work by Zenkin et al., he said, “This finding helps to explain the fidelity of gene transcription and suggests that self-correcting RNA was the genetic material during early evolution.”
    But how, exactly, could that have come about?  In his missing-link story, notice how many times Cramer used speculation words like could, probably and suggests compared to the hard requirements of reality:

The discovery of self-correcting RNA transcripts suggests a previously missing link in molecular evolution.  One prerequisite of an early RNA world (devoid of DNA) is that RNA-based genomes were stable.  Genome stability required a mechanism for RNA replication and error correction during replication, which could have been similar to the newly described RNA proofreading mechanism described by Zenkin et al.  If self-correcting replicating RNAs coexisted with an RNA-based protein synthesis activity, then an early RNA-based replicase could have been replaced by a protein-based RNA replicase.  This ancient protein-based RNA replicase could have evolved to accept DNA as a template, instead of RNA, allowing the transition from RNA to DNA genomes.  In this scenario, the resulting DNA-dependent RNA polymerase retained the ancient RNA-based RNA proofreading mechanism.
    Whereas an understanding of RNA proofreading is only now emerging, DNA proofreading had long been characterized. DNA polymerases cleave misincorporated nucleotides from the growing DNA chain, but the cleavage activity resides in a protein domain distinct from the domain for synthesis.  The spatial separation of the two activities probably allowed optimization of two dedicated active sites during evolution, whereas RNA polymerase retained a single tunable active site.  This could explain how some DNA polymerases achieve very high fidelity, which is required for efficient error correction during replication of large DNA genomes.

Of course, being only a “scenario” for how proofreading “could” have evolved, Cramer offered no evidence, lab or otherwise, for such a self-correcting RNA “missing link.”  For a discussion of problems with the RNA-world scenario, see the 07/11/2002 entry.

1Zenkin, Yuzenkova and Severinov, “Transcript-Assisted Transcriptional Proofreading,” Science, 28 July 2006: Vol. 313. no. 5786, pp. 518 – 520, DOI: 10.1126/science.1127422.
2Patrick Cramer, “Perspectives: Molecular Biology: Self-Correcting Messages,” Science, 28 July 2006: Vol. 313. no. 5786, pp. 447 – 448, DOI: 10.1126/science.1131205.

Was blindness ever so dark as to look design in the eye, and attribute it to mindless chance?  The blind see naught but their own imaginations.  Cramer took an incredibly wondrous phenomenon (imagine! self-correcting code) and weaved a purely fictional tale about how it emerged from The Ancient Soup.  Yet this is the myth that our culture only allows to be heard by students in public schools, because any other explanation, such as design, is classified as “religion” (along with, presumably, rocket-launching Hezbollah terrorism).  In the same issue of Science was a very positive book review of a new work about Richard Dawkins, the rabidly atheistic Darwinist who subscribes to the Ancient Soup myth or something very like it: reviewer David C. Queller says, “Dawkins spills his own dirty, obscene secret, again no less powerful now that we have known it for 30 years.  All flesh is survival machinery, and the survival it promotes is that of our selfish genes.”
    If this makes you angry, then it is time to take back science from the powers of darkness, obscenity, and selfishness that swept in like a flood after Darwin.  What would the original founders of the American Association for the Advancement of Science, like Joseph Henry, think of what has become of their honorable institution?

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Categories: Cell Biology, Genetics

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