Sid Altman

Molecular Biology

Discovered catalytic RNA, for which he won the Nobel Prize in 1989

"Don’t worry if things change. Just do what you do best."

Molecular biologists study the thousands of chemical reactions that go on inside cells to create and sustain life. Altman specializes in the chemical processes involved in copying information from DNA and using it to make proteins, the molecular building blocks of cells. Information is copied from DNA by the molecule RNA. About six different types of RNA are involved in this transcription process.

In Crick and Brenner’s lab, in about 1970, Altman was investigating part of this complex process. He discovered an enzyme called “RNase P” that chops a little “tail” off the end of an intermediate molecule of RNA called “precursor-tRNA.” Enzymes are special protein molecules that make chemical reactions go faster, a process called catalysis. Enzymes usually do this by holding or bending a molecule in a certain way so that one of its chemical bonds breaks easily. It took about 10 years, but Altman eventually discovered that the enzyme he was studying was not your average enzyme: instead of being a protein like all other enzymes, it was made of two parts — one strand of RNA and one protein. Furthermore, it was the RNA portion that provided the catalysis.

This was a significant discovery, because RNA molecules are much more primitive than protein molecules. Besides offering an explanation for how life might have begun billions of years ago before proteins existed, Altman’s discovery also hints at a way to beat a very troublesome primitive life form: the virus that causes the common cold. Cold viruses are made of RNA. It may be possible to design catalytic RNA-based vaccines that kill cold viruses by chopping up their RNA.

In recent years Dr. Altman and his research team at Yale University have applied their knowledge of RNA molecular biology to develop a method to inhibit the expression of any gene in any organism. They have patented a technique that stops the expression of virus genes in human tissue culture cells. Some day they expect it will work in vivo — in people.

The elucidation and understanding of the large role RNA plays in gene expression has expanded greatly since Altman’s discovery in the early 1980s. RNA employs a surprising variety of biochemical mechanisms that can result in different protein products coming from the same genetic code. “Tremendous amounts of different kinds of RNAs are now being identified,” says Altman. For instance, RNAi (or “interfering RNA”) regulates genes in microscopic worms called nematodes, as well as in plants and humans. It can turn genes on or off. These newly discovered powers of RNA are changing our concept of genes. We now know that, with the help of various types of RNA, a single gene can be interpreted in many different ways, leading to expression of various protein products. “It’s important, because 20 years ago we predicted this,” says Altman. It also helps explain how such a complex organism as a human being can arise from only about 30,000 genes.

3D model of M1 RNA. Click to enlarge.

A 3D model of M1 RNA, the catalytic RNA molecule that Altman discovered.

1. The t-RNA precursor molecule whose “tail” is chopped off by the catalytic RNA.

2. The arrow points to the site of cleavage where the t-RNA molecule is severed.

(Model produced with DRAWNA software by Eric Westhof, Institut de Biologie Moléculaire et Cellulaire, Centre National de la Récherche Scientifique, Strasbourg, France.)


ACTIVITY

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MYSTERY

Altman feels that perhaps the biggest mystery to be solved by the next generation will be the understanding of the human brain.

Explore Further

Bruce Alberts, et al., Molecular Biology of the Cell, fourth edition, Garland Science, 2001.

Altman's autobiography on the Nobel Prize website.

A video interview of Altman on the Nobel Prize website.

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