Friday, July 24, 2009

Tom Cech on catalytic RNAs

Tom Cech is someone that doesn’t need much of an introduction around here. Due to the "discovery of catalytic properties of RNA", he won the Nobel Prize in Chemistry in 1989 (along with Sidney Altman). Tom and his coworkers discovered self-splicing as a property of the pre-rRNA transcripts of the 26S rRNA gene from Tetrahymena: the intron was excised from the pre-rRNA and the exons were spliced together in vitro, in the absence of any protein1,2,3. In other words, the 26S rRNA precursor was able to splice itself in vitro.

We conclude that splicing activity is intrinsic to the structure of the RNA, and that enzymes, small nuclear RNAs and folding of the pre-rRNA into an RNP are unnecessary for these reactions. We propose that the IVS portion of the RNA has several enzyme-like properties that enable it to break and reform phosphodiester bonds. The finding of autocatalytic rearrangements of RNA molecules has implications for the mechanism and the evolution of other reactions that involve RNA.”1
This was the first example of a particular class of self-catalytic (self-excising) introns we now classify as “group I introns4.

I first met Tom at the Twelfth Annual Meeting of the RNA Society in 2007, where he gave the keynote lecture ("From the RNA world to the RNP world") and later on in Argentina in 2008, at a Gene Expression and RNA Processing meeting, where this picture was taken (back when I still wore my hair long).

Here’s a short interview by Richard Sever, where Tom discusses, very generally, RNA as a catalyst. He talks a little about the seminal discovery stated above, compares RNA- and protein-based catalysis and briefly discusses the evolution of catalytic RNAs.

I recommend that you download the video (rather than wait for it to load), as it is a 125Mb file.

1Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, Cech TR (1982) Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31(1):147-57

2 Inoue T, Sullivan FX, Cech TR.(1985) Intermolecular exon ligation of the rRNA precursor of Tetrahymena: oligonucleotides can function as 5' exons. Cell 43 2:431-7.

3 Sullivan FX, Cech TR. (1985) Reversibility of cyclization of the Tetrahymena rRNA intervening sequence: implication for the mechanism of splice site choice. Cell 42(2):639-48.

4 Some group I introns can self-splice in vitro, but almost all are thought to be assisted by proteins in vivo.

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