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From: cherry@husc4.UUCP
Newsgroups: sci.bio
Subject: Re: question - DNA's information
Message-ID: <1575@husc6.UUCP>
Date: Sat, 4-Apr-87 21:37:47 EST
Article-I.D.: husc6.1575
Posted: Sat Apr  4 21:37:47 1987
Date-Received: Sun, 5-Apr-87 13:44:00 EST
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Reply-To: cherry@husc4.harvard.edu (J. Michael Cherry)
Organization: Harvard Univ. Science Center
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>Let's make it clear that self-splicing RNAs mediate their splicing via
>intramolecular reactions. Once exons are spliced together, the reaction
>is over. By definition, a catalyst accelerates the rate of a chemical
>reaction without itself being consumed in the net reaction.
>Self-splicing RNAs are NOT catalytic. 
>
>The only examples I know of genuinely catalytic RNAs are: M1 RNA from
>E.coli, which has been elegantly shown by Sidney Altman & coworkers to
>accurately process the 5' termini of tRNAs in the absence of its
>physiological protein cofactor in vitro; M1 RNA-like molecules from
>Bacillus subtilis and other organisms; the Tetrahymena rRNA intron left
>over from the self-splicing of this transcript, which has been shown by
>T. Cech, et al, to possess RNA polymerase- and RNA restriction
>endonuclease-like activities in vitro.

The group I and II self-slicing RNAs, as well as the viroid RNAs, act on
part of themselves. However the work of Cech's group in Boulder and
Szostak's group in Boston have shown that the "enzyme" part of the group I
self-splicing introns (specifically the Tetrahymena rRNA sequence) is not
destroyed by the three reactions taking place in vivo but rather the
"substrate" part of the molecule is destroyed. Cech coined the term
ribozyme to designate these RNAs which perform the specific reactions
involved in the RNA splicing reaction. Generally they are considered not to
be catalysts by protein chemist because they only act once not because they
happen to cut themselves. In vitro these RNA molecules have been modified
by both Cech and Szostak to be true enzymes, acting on multiple substrate
molecules, not being changed by the reaction they catalyze, etc. 

Thus while it is true that in vivo the self-splicing RNAs are not catalytic
in the complete sense of the word they do carry out a reaction which would
not have happened without them. The change which occurs in one of these
RNAs is not the result of the ribozyme becoming involved as an intermediate
to the reaction but because the ribozyme cuts itself in a subsequent
reaction, it removes the recognition part of the enzyme. 

If these molecules can be enzymes in vitro, perhaps its just a matter of
time before more truely catalytic RNA molecules are discovered which act as
enzymes in vivo. 

Mike Cherry