Moss RNA editing systems work in human cells

(ORDO NEWS) — Specific RNA sequence editing systems called PPR65 and PPR56 have been transferred from moss mitochondria to human cells.

In a completely new environment, both turned out to be efficient, retained the accuracy of editing, and modified not only the target proteins, but also a number of others.

All living cells and “not quite alive” viruses work on the basis of a common principle – the so-called central dogma of molecular biology.

According to it, all the inherited traits of an organism are found in its DNA, which is “rewritten” into the language of RNA and then serves as a matrix for protein synthesis.

At the same time, DNA and RNA can be compared with texts or even instructions that are needed in order for the genome sequence to turn into a complex and self-regulating living being.

In the process of all this encryption and transfer of information, errors inevitably occur – that is, various mutations.

Although their certain frequency is acceptable and even necessary in the process of evolution, the cell still has to correct them – using various repair and editing mechanisms.

All this concerns not only the nuclear genome (if we are talking about eukaryotes that have it), but also some organelles – mitochondria that have their own genomes, and in the case of plants, also chloroplasts. Moreover, not only DNA can be modified, but also RNA created on its basis.

In different organisms, the mechanisms for editing one of the key biomolecules – ribonucleic acid, or RNA – can vary greatly.

The difference lies in which of the “letters” of the genetic code are chemically modified and how.

Thus, in the RNA of plant mitochondria and chloroplasts, cytidines (C) are converted into uridines (U), while in animal cells adenosines (A) become inosines (I), the latter occurring in much larger quantities.

It is not entirely clear how compatible these two types of editing are. The authors of a new paper in Nucleic Acid Research have drawn attention to two RNA editing systems that operate in plant cell organelles.

These are PPR65 and PPR56, named after the PPR RNA-binding proteins involved in them, which have special repeats in the sequence. They just carry out the chemical transformation of C into U, the so-called deamination.

At the same time, in the cytoplasm of plants (the main environment of the cell), such systems do not work. And in their mitochondria, PPR65 and PPR56 usually “correct” those errors in RNA that would have a particularly strong effect on protein structure.

Now, the researchers have transferred both systems from the mitochondria of the moss Physcomitrium patens into cultured human cells.

It turned out that in the new environment, PPR65 and PPR56 continue to work and retain their accuracy, eventually changing the sequence of not only the target proteins, but also a number of others.

In total, more than 900 different molecules turned out to be modified, and with an efficiency of up to 91% – and these are data only for PPR56.

The authors note the effectiveness of the PPR65 and PPR56 systems in the new environment and believe that they can become an alternative to the famous CRISPR-Cas gene editing system , for which the first biotechnological and medical applications have already been found.


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