Tuesday, January 06, 2015

The textbooks are wrong about protein synthesis according to a press release from the University of Utah

A recent paper in Science provides evidence that when protein synthesis is stalled a protein called Rqc2 ("conserved from yeast to man") catalyzes the addition of random amounts of alanine and threonine the the C-terminus of the proteins that's about to be destroyed (Shen et al., 2015).

Here's the editorial summary of the work ...
During the translation of a messenger RNA (mRNA) into protein, ribosomes can sometimes stall. Truncated proteins thus formed can be toxic to the cell and must be destroyed. Shen et al. show that the proteins Ltn1p and Rqc2p, subunits of the ribosome quality control complex, bind to the stalled and partially disassembled ribosome. Ltn1p, a ubiquitin ligase, binds near the nascent polypeptide exit tunnel on the ribosome, well placed to tag the truncated protein for destruction. The Rqc2p protein interacts with the transfer RNA binding sites on the partial ribosome and recruits alanine- and threonine-bearing tRNAs. Rqc2p then catalyzes the addition of these amino acids onto the unfinished protein, in the absence of both the fully assembled ribosome and mRNA. These so-called CAT tails may promote the heat shock response, which helps buffer against malformed proteins
This is mildly interesting. We've known about ubiquitin ligase for decades but this is a different way of tagging proteins for destruction.

We'll have to see if this work stands up to verification but even if it does, it's not going to make it into the textbooks.

Let's see what the University of Utah Press Office has to say ...
Defying Textbook Science, Study Finds New Role for Proteins

Open any introductory biology textbook and one of the first things you’ll learn is that our DNA spells out the instructions for making proteins, tiny machines that do much of the work in our body’s cells. Results from a study published on Jan. 2 in Science defy textbook science, showing for the first time that the building blocks of a protein, called amino acids, can be assembled without blueprints – DNA and an intermediate template called messenger RNA (mRNA). A team of researchers has observed a case in which another protein specifies which amino acids are added.

"This surprising discovery reflects how incomplete our understanding of biology is,” says first author Peter Shen, Ph.D., a postdoctoral fellow in biochemistry at the University of Utah. “Nature is capable of more than we realize." ...
Mathew Cobb, writing on Jerry Coynes blog, explains why this isn't really a big deal [CAT tails weaken the central dogma – why it matters and why it doesn’t]. Let me just add that the synthesis of peptides with defined sequences in the absence of mRNA and ribosomes has been described in most textbooks since the 1980s. The best examples are the peptides involved in pepditogylcan synthesis (cell walls) and peptide antibiotics.

Here's a figure from my book.


What this means is that the statement, "... showing for the first time that the building blocks of a protein, called amino acids, can be assembled without blueprints – DNA and an intermediate template called messenger RNA (mRNA)" is simply not true.

We really, really, need to do something about university press releases.


Shen, P.S., Park, J., Qin, Y., Li, X., Parsawar, K., Larson, M.H., Cox, J., Cheng, Y., Lambowitz, A.M., Weissman, J.S., Brandman, O., and Frost, A. Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains. Science 347:75-78. [doi: 10.1126/science.1259724 ]

9 comments :

  1. Not a fan of the title of Matthew Cobb's post. CAT tails don't have anything to do with the Central Dogma. The alanine and threonine are added at random, in no particular order, therefore there is no sequence information associated with the CAT tail.

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    1. Agree. While Matthew displays proper perspective on the Central Dogma it is ultimately much ado about nothing as the enzyme activity has nothing to do with CD concept.

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  2. "Let me just add that the synthesis of peptides with defined sequences in the absence of mRNA and ribosomes has been described in most textbooks since the 1980s."

    But Larry, Quest has explained over and over that you can't make protein without DNA and you can't make DNA without protein! Oh, you think you know more than a creationist just because you teach the subject?

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  3. We really, really, need to do something about university press releases.

    Agreed. Maybe hold the researchers responsible for them?

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    1. I think the problem is two-fold unfortunately. Sometimes scientists and/or the press offices. Bold claims are easy publicity for the university, but also some scientists make bold claims as they try dumb down the science.

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    2. Joe: "Maybe hold the researchers responsible for them?"

      I got a real idea.

      How about if Larry and the readers of this blog hold an awards contest for the most exaggerated BS press release of the year.

      Call it the Pressiopath Award. Make it a golden cow turd, and award it, NOT to the offending university's press office, but to the scientists whose work was being touted. Hold them responsible. They get the golden turd.

      Delete
    3. Not too familiar with nature of university press offices, but I would doubt there is anyone in such an office that would be knowledgable enough regarding mol biology to construct such a press release without a great deal of help from the researchers themselves.

      Delete
  4. But the amino acid chains of peptidoglycan and peptide antibiotics are assembled by sets of dedicated enzymes, entirely independent of ribosomes.

    Is this the first example of non-templated synthesis of an amino-acid chain by the ribosomal protein synthesis machinery?

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  5. There have been some really interesting University press releases recently which have attracted criticism from reputable publishers. However, they did point out that the problem is also sometimes the researchers selling claims (or dumbing the science down to much) that are just not true. Either way, scientists really need to keep their press offices in line and press offices really need to do fact checking. Its after all a form of journalism and it should be unbiased and ethical.

    Good post.

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