Unintelligent Designer News - A Moss RNA Repair Mechanism That also Works in Human Cells

Moss repair team also works in humans — University of Bonn

The editor PPR56, - which only acts in mitochondria in the moss, edits more than 900 different positions in nuclear transcripts in human cells. The size of the respective nucleotide (A, U, C, G) shows how often it occurs at this position of the targets additionally edited by PPR56 in the human transcripts.

© Elena Lesch/University of Bonn

If ever a scientific discovery was designed to embarrass Creationist's, this is it. It is the discovery by scientists at the University of Bonn, Germany, that an RNA editing process which is normally used in plant mitochondria and chloroplasts, works in animal cells, including human cells.

What the scientists discovered is that if they transfer the RNA editing machines PPR56 and PPR65 from moss into human cells, they still work and edit RNA as they would in plants cells.

The process repairs mistakes in the RNA transcribed from the DNA. Although the mistakes are in the RNA, they are correct transcriptions of mistakes in the DNA itself. The mistakes in the DNA are left alone - which means they accumulate over the generations. In animal cells DNA is repaired (albeit imperfectly) when the cell is replicated, but not so in plant mitochondria and chloroplasts.

Now, there may be advantages in allowing mistakes to accumulate over time because this means there are more mutations for natural selection to work on so giving the organelles more evolvability. However, since the transcribed RNA is repaired, this doesn't seem to be an explanation because the resulting proteins will be the same, regardless.

Overview of Transcription - Khan Academy

What plant organelles have ended up with is the equivalent of a master document which it to be photocopied lots of times, but which has spelling mistakes in it. Then, instead of correcting the master copy, each photocopy is scanned for mistakes and corrected, while the mistakes are left in the master copy. When a new master copy is needed, it is made by copying the old master copy, mistakes and all, and any new mistakes intoduced in that process also go unrepaired.

On the face of it, this doesn't seem to be a process that could be described as intelligently designed!

As the University of Bonn news release explains:

Moss repair team also works in humans

Researchers at the University of Bonn transplant RNA editing machine of a moss into human cells

If everything is to run smoothly in living cells, the genetic information must be correct. But unfortunately, errors in the DNA accumulate over time due to mutations. Land plants have developed a peculiar correction mode: they do not directly improve the errors in the genome, but rather elaborately in each individual transcript. Researchers at the University of Bonn have transplanted this correction machinery from the moss Physcomitrium patens into human cells. Surprisingly, the corrector started working there too, but according to its own rules. The results have now been published in the journal "Nucleic Acids Research".

In living cells, there is a lot of traffic like on a large construction site: In land plants, blueprints in the form of DNA are stored not only in the cell nucleus, but also in the cell’s power plants (mitochondria) and the photosynthesis units (chloroplasts). These blueprints contain building instructions for proteins that enable metabolic processes. But how is the blueprint information passed on in mitochondria and chloroplasts? This is done by creating transcripts (RNA) of the desired parts of the blueprint. This information is then used to produce the required proteins.

Errors accumulate over time

However, this process does not run entirely smoothly. Over time, mutations have caused errors to accumulate in the DNA that must be corrected in order to obtain perfectly functioning proteins. Otherwise, the energy supply in plants would collapse. At first glance, the correction strategy seems rather bureaucratic: instead of improving the slip-ups directly in the blueprint - the DNA - they are cleaned up in each of the many transcripts by so-called RNA editing processes.

Why living cells make this effort, we do not know. Presumably, these mutations increased as plants spread from water to land during evolution.

Dr. Mareike Schallenberg-Rüdinger, co-senior author
Institute of Cellular and Molecular Botany (IZMB)
University of Bonn, Bonn, Germany.

Compared to letterpress printing, it would be like correcting each individual book by hand, rather than improving the printing plates.

In 2019, the IZMB team led by Prof. Dr. Volker Knoop succeeded in transplanting RNA editing processes from the moss Physcomitrium patens into the bacterium Escherichia coli. It was shown that the repair proteins of the moss can also modify the RNA of these bacteria.

Our results showed that the land plant correction mechanism also works in human cells. This was previously unknown.

Elena Lesch, first author
Institute of Cellular and Molecular Botany (IZMB)
University of Bonn, Bonn, Germany.

Now, researchers from the Institute of Cellular and Molecular Botany, together with the team led by Prof. Dr. Oliver J. Gruss from the Institute of Genetics at the University of Bonn, have gone one step further: They transferred the RNA editing machinery from the moss into standard human cell lines, including kidney and cancer cells, for example.

But that's not all: the RNA editing machines PPR56 and PPR65, which only act in mitochondria in the moss, also introduce nucleotide changes in RNA transcripts of the cell nucleus in human cells.

More than 900 targets

Surprisingly for the research team, PPR56 makes changes at more than 900 points of attack in human cell targets. In the moss, on the other hand, this RNA corrector is only responsible for two correction sites." There are many more nuclear RNA transcripts in human cells than mitochondrial transcripts in the moss," explains Dr. Mareike Schallenberg-Rüdinger. "As a result, there are also many more targets for the editors to attack." Although the editors follow a particular code, at this stage, it is not yet possible to accurately predict where the editing machines will make changes in human cells.

However, the abundance of RNA editing targets in human cells also offers the opportunity to find out more about the basic mechanisms of the correctors in further studies. This could be the basis for methods of inducing a very specific change in RNA in human cells by means of a corrector. "If we could correct faulty sites in the genetic code with RNA editing methods, this would potentially also offer starting points for the treatment of hereditary diseases," says Schallenberg-Rüdinger, looking to the future. "Whether that will work remains to be seen."

Copyright: © 2022 The authors.
Published by Oxford University Press on behalf of Nucleic Acids Research. Open access. (CC BY 4.0)

The team have published their findings in an open access paper in the journal Nucleic Acids Research:

Abstract

RNA editing processes are strikingly different in animals and plants. Up to thousands of specific cytidines are converted into uridines in plant chloroplasts and mitochondria whereas up to millions of adenosines are converted into inosines in animal nucleo-cytosolic RNAs. It is unknown whether these two different RNA editing machineries are mutually incompatible. RNA-binding pentatricopeptide repeat (PPR) proteins are the key factors of plant organelle cytidine-to-uridine RNA editing. The complete absence of PPR mediated editing of cytosolic RNAs might be due to a yet unknown barrier that prevents its activity in the cytosol. Here, we transferred two plant mitochondrial PPR-type editing factors into human cell lines to explore whether they could operate in the nucleo-cytosolic environment. PPR56 and PPR65 not only faithfully edited their native, co-transcribed targets but also different sets of off-targets in the human background transcriptome. More than 900 of such off-targets with editing efficiencies up to 91%, largely explained by known PPR-RNA binding properties, were identified for PPR56. Engineering two crucial amino acid positions in its PPR array led to predictable shifts in target recognition. We conclude that plant PPR editing factors can operate in the entirely different genetic environment of the human nucleo-cytosol and can be intentionally re-engineered towards new targets.

Graphical Abstract

Plant mitochondrial PPR-DYW deaminase specifically edits cytidines in nuclear-cytosolic transcripts in human cells. The editing enzyme can be re-directed to new targets via modification of single binding motifs.

Elena Lesch, Maximilian T Schilling, Sarah Brenner, Yingying Yang, Oliver J Gruss, Volker Knoop, Mareike Schallenberg-Rüdinger
Plant mitochondrial RNA editing factors can perform targeted C-to-U editing of nuclear transcripts in human cells
Nucleic Acids Research, 2022;, gkac752, https://doi.org/10.1093/nar/gkac752

Copyright: © 2022 The authors.
Published by Oxford University Press on behalf of Nucleic Acids Research. Open access
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

This raises several problems for Creationists, especially those who believe an intelligent [sic] designer is responsible for these processes:

1. Why is this not evidence of a common origin of plants and animals?
2. Why would an intelligently designed process by an omnipotent, omniscient designer result in mistakes that need repairing?
3. Why would an intelligent designer use such an unncessarily complicated process to correct the mistakes in DNA replication when it uses a simpler process in animal cells, which doesn't mean mistakes continue to accumulate in the Genome?
4. If there are no advantages in carrying out the repair at the RNA level instead of at the DNA level, why 'design' two different processes to achieve the same result?
5. If there are advantages, why not use the advantageous process for animals as well as plant organelles?

No doubt all those problems will be waved aside with the ultimate in non-answer, "God works in mysterious ways!", whilst still insisting that intelligent [sic] design is real science, not religion in a lab coat.