Decaying RNA molecules tell a story

Decaying RNA molecules tell a story
The enzyme that degrades messenger RNA follows the ribosomes and stops every 3 nucleotides. Credit: V.Pelechano/EMBL

Once messenger RNA (mRNA) has done its job - conveying the information to produce the proteins necessary for a cell to function - it is no longer required and is degraded. Scientists have long thought that the decay started after translation was complete and that decaying RNA molecules provided little biological information.

Now a team from EMBL Heidelberg and Stanford University led by Lars Steinmetz has turned this on its head in an article published in Cell. The researchers have shown that one end of the mRNA begins to decay while the other is still serving as a template for protein production. Thus, studying the decaying mRNA also provides a snapshot of how proteins are produced.

The discovery was made almost by accident. As part of research into how DNA is transcribed into mRNA, co-researchers Vicent Pelechano and Wu Wei developed an in vivo method to count decaying mRNA molecules in the cell. mRNA has a protective 'cap' that prevents it from being degraded - once that cap is removed, the decay begins. The researchers spotted a pattern in the distribution of the 'cap-less' RNA that they didn't expect.

Vicent Pelechano, from the Steinmetz group at EMBL Heidelberg, explains: "The decaying RNA was thought to be of little interest biologically, so we were really surprised to see a pattern. We looked more deeply into it because it appeared to be linked to the genetic code, but we never expected it to lead to a completely new understanding of how mRNA and interact."

Proteins are produced from mRNA by ribosomes - 'molecular machines' that pass successively along the mRNA to translate its nucleotides into amino acids. It was thought that the mRNA only started to decay once the final ribosome had left it and translation was complete. In fact, the researchers were able to determine that the protective 'cap' is removed and degradation begins even while ribosomes are still associated with the mRNA.

They demonstrated that the enzyme degrading mRNA follows closely behind the ribosome, pausing at set points along the mRNA, usually after each group of 3 nucleotides, the section of code that relates to one amino acid. The team believes that this shows the enzyme pausing while translation goes on - allowing the ribosome to do its work and move on - before starting to degrade the mRNA previously protected by the ribosome.

This novel approach also opens up new avenues to study ribosomes. "Researchers studying ribosome activity usually use drugs to stall the ribosomes in place. This can alter the way we perceive their activity. We are simply looking for the molecules remaining from mRNA decay and determining their distribution. We believe this shows a more accurate picture of what is happening to the mRNA and the ribosome than was previously possible," explains Wu Wei of Stanford University.


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It's not always the DNA: Damaged messenger RNA can jam cellular machines that make protein

Journal information: Cell

Citation: Decaying RNA molecules tell a story (2015, June 4) retrieved 15 October 2019 from https://phys.org/news/2015-06-rna-molecules-story.html
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JVK
Jun 05, 2015
Excerpt: Proteins are produced from mRNA by ribosomes - 'molecular machines' that pass successively along the mRNA to translate its nucleotides into amino acids.

Mutations perturb that translation. Nutrient-dependent microRNAs link RNA-mediated amino acid substitutions to the stability of organized genomes via the physiology of reproduction in all genera.

Jun 05, 2015
Mutations perturb that translation.


Depends. If a codon is mutated to a stop codon, it will stop prematurely, but otherwise it'll go along normally following the altered sequence.

Whether a mutation perturbs anything depends on where it is and what type of substitution it is. Threonine and serine, for instance, may behave similarly when substituted for one another because of their R group similarity.

JVK
Jun 05, 2015
What enabled the amino acid substitutions and fixed them in the organized genomes of the organisms that you think evolved?

Where did the amino acids that were substituted come from? Does any experimental evidence link the substituted amino acids to a last universal common ancestor. If not, how did evolution via mutations occur?

Jun 06, 2015
What enabled the amino acid substitutions


Not exactly sure what you mean by this. Amino acids are determined by DNA codons. If a codon changes, the amino acid that position codes for changes. Example- if ACA gets changed to AAA, a lysine will be coded for instead of a threonine.

https://www2.le.a...able.jpg

Fixation can occur through many different mechanisms. Strong selection, genetic bottlenecks, genetic drift, etc. These are all easy enough to demonstrate experimentally using something like Drosophila.

Where did the amino acids that were substituted come from?


Vague question. Are you talking about the initial origin of amino acids or where current organisms get theirs from?

Does any experimental evidence link the substituted amino acids to a last universal common ancestor.


Another weirdly worded, vague question. Can you reword this and be more specific?

JVK
Jun 06, 2015
Vague question. Are you talking about the initial origin of amino acids or where current organisms get theirs from?


Another weirdly worded, vague question. Can you reword this and be more specific?


The light-induced de novo creation of amino acids links RNA-mediated cell type differentiation via nutrient-dependent amino acid substitutions and the physiology of reproduction in all genera. I cannot be more specific. I tell you that, ask:

1) Where did the amino acids that were substituted come from?

Your answer should be: I am a biologically uniformed science idiot, and have no idea where amino acids come from.

2) Does any experimental evidence link the substituted amino acids to a last universal common ancestor.

Your answer should be: I am a biologically uninformed science idiot who does not know there is no link from amino acid substitutions to a last universal common ancestor.

Your answer: Can you...be more specific? NO, I detailed the facts

Jun 06, 2015
If you're referring to the original origin of amino acids, there is a lot of experimental work on prebiotic synthesis.

http://www.nature...769.html

Does any experimental evidence link the substituted amino acids to a last universal common ancestor.


Still doesn't make much sense. This is another case of you using "link" where something more relevant could go. Are you asking if substituted amino acids are evidence of a LUCA?

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