For many years, the evolution of protein production (called translation) seemed like a bit of a chicken-and-egg problem. The complex that catalyzes translation, the ribosome, contains both RNA and proteins, which causes a bit of a paradox: how did the first proteins get made if their production required the ribosome's proteins? Decades ago, Francis Crick had suggested a simple solution, where the chemical reactions that link a chain of amino acids into a protein were catalyzed by RNA. But for many years this suggestion was largely ignored, as many assumed that the ribosomal RNA did little more than act as scaffolding for the complex's proteins.

But over time, bits of biochemical evidence suggested Crick might have been on to something, as they hinted that the ribosomal RNA might be a bit more than inert scaffolding. Ultimately, the conclusive evidence came when researchers finally determined the structure of an intact ribosome, and located the active site. There were no proteins at the site, simply RNA.

Two of the people honored with Nobel Prizes for determining the structure of the ribosome were at the Lindau Meeting (Ada Yonath and Thomas Steitz), and they spoke for a bit about the long and sometimes challenging work that eventually got them the ribosome's structure. But it was the structure itself that was really the star of their presentations.

In this image, the protein components of the ribosome are shown in yellow; its RNA is in grey. What should be obvious is that the image of rRNA as a scaffold for proteins has it exactly backwards. Instead, the proteins are simply sprinkled across the surface of a massive RNA that is the primary component of the ribosome. Now, it should have been possible to figure out the relative sizes of the molecules involved here and make the prediction that this was the more probable picture. But, in the absence of the structure, it's not obvious that people would have really found these sorts of arguments compelling.

With additional structures, it was possible to catch snapshots of the ribosome at work. Steitz showed these in video form, complete with a soundtrack that had the audience bursting out laughing.

With the progress we've had in building our own catalytic RNAs, some of the details here aren't really surprising: base pairing helps line up the tRNA that carries an amino acid into the reaction, another base interacts with the amino acid directly to position it properly, and parts of a sugar on the RNA backbone helps drive the actual catalytic step. But some of these structures are well over a decade old, so they were more of a surprise when they first came out.

The structure has told us a lot about the ribosome, but it's probably told us more about the origin of life. The first catalytic RNAs has led to the hypothesis that there might once have been an RNA world that existed before there were proteins, where genetic information and catalytic activity were combined in a single molecule. The key role of RNA in the ribosome obviously hints that it was probably once performing translation without the help of any proteins whatsoever. And that in turn indicates that RNA isn't limited to catalyzing the simple, one-off reactions that are typical of the ones we've been producing. In the ribosome, RNA can form large cooperative complexes, run through a complex catalytic cycle, and generate products that are essential to life.

If you read through the above, two themes should be apparent. One is that we didn't absolutely need the structure of the ribosome to figure all of this out; a lot of it could be reasoned or pieced together from bits of information gathered in other experiments. But the second theme is that the structure of the ribosome, in a conclusive and visual way, made all of those arguments far more compelling, and brought the reasoning to a decisive end.

Although Steitz and Yonath mostly focused on the history of their work in obtaining this structure, their work is so compelling that just a few pictures and a short video were able to tell the audience a lot about the history of all life on Earth.

Listing image by Illustration by Aurich Lawson