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Vol. 96, Issue 1, 173-178, January 5, 1999 (2',5'-link / prebiotic / manganese / RNA
editing / ribozyme)
Department of Ecology and Evolutionary Biology, Princeton
University, Princeton, NJ 08544
Communicated by Thomas E. Shenk, Princeton University, Princeton,
NJ, October 26, 1998 (received for review August 7, 1998)
In vitro selection, or directed molecular
evolution, allows the isolation and amplification of rare sequences
that satisfy a functional-selection criterion. This technique can be
used to isolate novel ribozymes (RNA enzymes) from large pools of
random sequences. We used in vitro evolution to select a
ribozyme that catalyzes a novel template-directed RNA ligation that
requires surprisingly few nucleotides for catalytic activity. With the exception of two nucleotides, most of the ribozyme contributes to a
template, suggesting that it is a general prebiotic ligase. More
surprisingly, the catalytic core built from randomized sequences actually contains a 7-nt manganese-dependent self-cleavage motif originally discovered in the Tetrahymena group I intron.
Further experiments revealed that we have selected a dual-catalytic RNA from random sequences: the RNA promotes both cleavage at one site and
ligation at another site, suggesting two conformations surrounding at
least one divalent metal ion-binding site. Together, these results
imply that similar catalytic RNA motifs can arise under fairly simple
conditions and that multiple catalytic structures, including
bifunctional ligases, can evolve from very small preexisting parts. By
breaking apart and joining different RNA strands, such ribozymes could
have led to the production of longer and more complex RNA polymers in
prebiotic evolution.
Copyright © 1999 by The National Academy of Sciences 0027-8424/99/96173-6$2.00/0
Evolution
Emergence of a dual-catalytic RNA with metal-specific cleavage
and ligase activities: The spandrels of RNA evolution
*
To whom reprint requests should be addressed. e-mail:
lfl{at}princeton.edu.
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