Researchers design first artificial ribosome

July 29, 2015 by Sam Hostettler

Researchers at the University of Illinois at Chicago and Northwestern University have engineered a tethered ribosome that works nearly as well as the authentic cellular component, or organelle, that produces all the proteins and enzymes within the cell. The engineered ribosome may enable the production of new drugs and next-generation biomaterials and lead to a better understanding of how ribosomes function.

The artificial ribosome, called Ribo-T, was created in the laboratories of Alexander Mankin, director of the UIC College of Pharmacy's Center for Biomolecular Sciences, and Northwestern's Michael Jewett, assistant professor of chemical and biological engineering. The human-made ribosome may be able to be manipulated in the laboratory to do things natural ribosomes cannot do.

When the cell makes a , mRNA (messenger RNA) is copied from DNA. The ribosomes' two subunits, one large and one small, unite on mRNA to form the functional unit that assembles the protein in a process called translation. Once the protein molecule is complete, the ribosome subunits—both of which are themselves made up of RNA and protein—separate from each other.

In a new study in the journal Nature, the researchers describe the design and properties of Ribo-T, a ribosome with subunits that will not separate. Ribo-T may be able to be tuned to produce unique and functional polymers for exploring ribosome functions or producing designer therapeutics—and perhaps one day even non-biological polymers.

No one has ever developed something of this nature.

"We felt like there was a small—very small—chance Ribo-T could work, but we did not really know," Mankin said.

Mankin, Jewett and their colleagues were frustrated in their investigations by the ribosomes' subunits falling apart and coming together in every cycle of protein synthesis. Could the subunits be permanently linked together? The researchers devised a novel designer ribosome with tethered subunits - Ribo-T.

"What we were ultimately able to do was show that by creating an engineered ribosome where the ribosomal RNA is shared between the two subunits and linked by these small tethers, we could actually create a dual translation system," Jewett said.

"It was surprising that our hybrid chimeric RNA could support assembly of a functional ribosome in the cell. It was also surprising that this tethered ribosome could support growth in the absence of wild-type ribosomes," he said.

Ribo-T worked even better than Mankin and Jewett believed it could. Not only did Ribo-T make proteins in a test-tube, it was able to make enough protein in bacterial cells that lacked natural to keep the bacteria alive.

Jewett and Mankin were surprised by this. Scientists had previously believed that the ability of the two ribosomal subunits to separate was required for protein synthesis.

"Obviously this assumption was incorrect," Jewett said.

"Our new protein-making factory holds promise to expand the genetic code in a unique and transformative way, providing exciting opportunities for synthetic biology and biomolecular engineering," Jewett said.

"This is an exciting tool to explore ribosomal functions by experimenting with the most critical parts of the machine, which previously were 'untouchable,'" Mankin added.

Explore further: Mimicking living cells: Synthesizing ribosomes

More information: Nature, DOI: 10.1038/nature14862

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Torbjorn_Larsson_OM
3.7 / 5 (3) Jul 30, 2015
The bottom part of a ribosome serves as a clamp, and besides possible regulatory functions I think it is all it does. Presumably the evolved 2 part system is a frozen accident that shows the ribosome didn't evolve as a RNA-protein translator in toto, but was coopted from the use of its upper part function, producing polypeptide chains.

That makes sense, the code would evolve gradually. (Some amino acids are coded for by 6 triplets and presumably were coded for first, some with only 1 triplet so were squeezed in with no redundancy as the end of code evolution.) The initial ribosome then produced random peptide chains, that could have found use as cofactors and nests for early metal/metal sulfide catalysts.
FredJose
1 / 5 (5) Jul 30, 2015
Presumably the evolved 2 part system is a frozen accident that shows the ribosome didn't evolve as a RNA-protein translator in toto

It's highly unlikely that the separating two-part ribosome could have "evolved" because it is necessary for life. If there is no life, then there cannot be any "evolution".
Futhermore, it's not possible for some random chemical/physical process to create life as we know it. Hoyle and Wikramasinghe has already shown that to be the case and people are still falling over their own feet trying to find a solution to the vexing conundrum of life arising from dead materials all by itself.

So far there is no solution to the problem and frankly from the knowledge we have of chemistry, physics, biology, statistics and information science, the possibilities of life arising from said dead materials all by itself is vanishingly small. So small in fact as to indicate it's simply impossible. That's why Wikramasinghe is an ardent believer in Panspermia.
FredJose
1 / 5 (5) Jul 30, 2015
That makes sense, the code would evolve gradually.

How can code "evolve" in the living cell? To what end would it be "evolving"?
For the code to be useful, there needs to be a decoder that understands and makes the code useful. Therefore the decoder needs to be co-developed simultaneously with the code - which is anathema to the idea of things "slowly evolving in a step-by-step fashion". Any process involving a simultaneous independent development of complimentary code/decoder screams of foreknowledge and therefore of design. So the code/decoder paradigm rules out any thought of those things "evolving".
Eikka
5 / 5 (5) Jul 30, 2015
If there is no life, then there cannot be any "evolution".


Evolution doesn't depend on life. Any system that changes by replication, alteration and selection is undergoing evolution, whether it is alive or not.

That's why Wikramasinghe is an ardent believer in Panspermia.


Panspermia is simply pushing the problem out of sight. It doesn't explain the event.

For the code to be useful, there needs to be a decoder that understands and makes the code useful.


The chemicals, nucleotides that form RNA and DNA are in themselves chemically active and react spontaneously with one another and other substances. They are not merely abstract and inert information, as is understood by "code" in the sense of computer code, and therefore a "decoder" is not strictly necessary for them to perform a function.

The cell is not some archetypical computer that is running a ticker tape made out of DNA.
Torbjorn_Larsson_OM
5 / 5 (1) Jul 31, 2015
@FredJose: " If there is no life, then there cannot be any "evolution"."

That is obviously wrong. Mechanisms such as selection works on autocatalytic cycles too.

There is - of course - no hard line between "life" and "non-life" anymore than there is between species in later evolution. It takes time before such separation occur in evolutionary processes. (Gradual survivable change, remember.)

"it's not possible for some random chemical/physical process to create life as we know it."

Ha! That is so wrong so it is laughable.

First off, evolution is not random, because selection isn't entirely. (It is precisely deterministic in infinitely large populations.) Second, we know early Earth was sterile, and we know late Earth is non-sterile. Hence life emerged, and was never infinitely old.

Third, we now know that the ancestor to the UCA lineage likely was Hadean alkaline hydrothermal vents, due to the phylogenetic evidence. This is no large mystery anymore.

[tbctd]
Torbjorn_Larsson_OM
5 / 5 (1) Jul 31, 2015
[ctd]

"Wikramasinghe".

So? He is a recognized nut creationist and conspiracy theorist. But we are discussing science here.

"How can code "evolve" in the living cell? To what end would it be "evolving"?"

Huh? To what end does a stone fall to the floor? What is its purpose of falling, or what is the purpose of the existence of stones or gravity? Gravity and evolution are processes, and processes observably happens in physics.

If you want to discuss "ends", prove them first. Same if you want to discuss other purported traits of your preferred magic. Show us the money!

Meanwhile we can discuss science, that what actually is. But as already my first comment described code evolution, I am not going to repeat just because you were too lazy to read before posting.

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