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February 20, 2009

Deconstructing the Ribosome

Our lives depend on a microscopic tangle of molecules called the ribosome. The job of the ribosome is to use the sequence of DNA in a gene to build a corresponding protein. Other enzymes first build a single-stranded copy of the gene from RNA, and then a ribosome grabs onto the RNA and "reads" it, using the information to decide which building block to grab next in order to build a protein. (Here's a video of the process.)

The ribosome has two parts that come together around the RNA like a pair of jaws, and each one is a fiendish nest of complexity. Each of the jaws, known as subunits, is a mix of protein and RNA. This animation, created by David S. Goodsell, shows the structure of the large subunit in bacteria. It contains two RNA molecules in it, a big one here colored orange, and a small one colored yellow. The proteins wrapped around them are in blue. The big RNA molecule alone is a marvelous migraine of complexity. It measures 2900 nucleotides long, and it twists and folds in on itself again and again to form the supreme Gordian knot.

All living things make ribosomes and use them for the same essential purpose. It is a sign of our common heritage with baobabs and starfish, with plague and mold. But the fact that the ribosome is everywhere makes its evolution difficult to study. There is no partial ribosome in nature to offer clues to how it emerged. But in this article in the 19 February issue of Nature, Konstantin Bokov and Sergey Steinberg, two biochemists from the University of Montreal, offer some new hope: It's possible that the evolution of the ribosome is recorded in its very own tangles.

Bokov and Steinberg show that the ribosome is like an onion, with outer layers that can be peeled away from inner ones. The proteins of the ribosome help keep it stable, but they themselves do not actually weld together new proteins. That's the work of the ribosomal RNA. As I wrote in my January Origins essay, many researchers now argue that DNA and proteins were not the first biological molecules to emerge; before they existed, life was based on RNA alone. The origin of the ribosome, Bokov and Steinberg argue, is really the origin of the ribosomal RNA.

Ribosomal RNA is made up of dozens of loops, and loops upon loops, all folded in on each other. But Bokov and Steinberg point out that they have an onionlike order of their own. They inspected all the loops, looking for ones that could be removed without altering the rest of the RNA molecule. They found 19 of these expendable loops. Next, they looked at the loops that had kept those 19 loops stable but which could be eliminated without affecting the rest of the RNA. They found 11 such loops. Below these two layers, Bokov and Steinberg found yet another layer of loops, and another, and another, until they had reduced the ribosomal RNA to a tiny fragment, a core on which all the rest depended.

Bokov and Steinberg propose that the seeming complexity of the ribosome is something of a mirage. Its evolution was actually pretty simple. It evolved from a tiny piece of RNA, perhaps only 110 nucleotides long. At first, this molecule didn't build proteins; it may have carried out some kind of reaction on other RNA molecules in RNA-based cells. Then mutations accidentally duplicated the fragment, building new units that could fold back on the older units. This protoribosome may have been able to add random building blocks together. New layers of loops evolved, making the ribosome more precise, able to build specific proteins when it read specific pieces of RNA. Newer loops made the ribosome even more stable and thus able to crank out proteins even faster. The last major step in the evolution of the ribosome was the addition of its proteins.

The most practical way to test Bokov and Steinberg's hypothesis will be to build the intermediate ribosomes and see if they work as predicted. But perhaps we should not give up on nature just yet. As I have reported, RNA-based life could conceivably still be hiding in refuges somewhere here on Earth, eking out an existence with ribosomes that are a little less hideous than our own.

Carl Zimmer

4 Comments

@ David:

Thank you for your answer. That clears things up and straightens out a potential misunderstanding on my part. See, I had a sense that, because of its functionality, RNA might be comparable to a bacterium (if only very loosely). Your answer helps my comprehension of the subject tremendously.

James, what do you mean by "self-motivated"? RNA most certainly is mere matter being pushed around by its environment. Even the direction in which a bacterium swims is completely mechanistically determined by its environment. Without a nervous system, motivation doesn't even enter into the question, as far as I can tell.

nosivad, when you contradict a well-argued blog post, why don't you explain why you contradict it? What purpose is that supposed to have?

The ribosome never "evolved." It first appeared in its present form. The same can be said for every other intracellular organelle.

I am curious as to what, at this level of life, is mechanistically driven and what is, in the loose but specific sense, self-motivated. From what I've gleaned reading up on research on abiogenesis, RNA is beyond mere matter being pushed around by its environment, but is certainly not alive in the sense an amoeba is.

How does RNA compare to, say, an RNA virus, in terms of whether it is considered "living" or not?

Please forgive my general ignorance here. I am teaching myself about all this without the benefit of a professor of biology to help me, and the terms "life", "living" and "alive" are feeling pretty vague to me right about now w/r/t abiogenesis.

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