RNA editing

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RNA editing (from English), German RNA editing or RNA editing , is a biochemical process within certain cells or cell organelles that can take place in the course of gene expression and that changes the reproduction of genetic information.

Here, after the transcription and before a translation, the nucleotide sequence of the transcript is changed with regard to individual nucleobases of the messenger RNA ; it then no longer corresponds to the original genomic nucleotide sequence of the DNA. RNA editing is an important form of post- transcriptional modification (see RNA processing ). In addition to the (kotranskriptionellen) splicing ( English splicing ) the by RNA editing a diversity of transcriptome increased and thus a significantly higher protein enables diversity.

In the case of RNA editing, a basic distinction is made between processes in which single or multiple nucleotides are inserted or removed from the RNA, which is called insertion / deletion editing , and those in which individual nucleobases or riboses of an RNA strand are chemically modified, for example a deamination of adenosine (A) to inosine (I) or a conversion of uridine (U) to pseudouridine (Ψ), which is also called RNA modification .

RNA editing in trypanosomes

Insertion and deletion editing occurs to a large extent in mitochondria of trypanosomes (organisms that are also characterized by another unusual form of RNA processing, trans-splicing ). Almost every second uracil nucleotide (uridine) of the mitochondrial mRNAs is inserted into the primary transcript with the help of the so-called "editosome". Guide RNAs play an important role here; they ensure the specificity of the editosome and the insertion of the correct number of Us (uridine units, cf. snoRNAs , which fulfill a similar function).

RNA editing in higher eukaryotes

In higher eukaryotes such as B. mammals , on the other hand, is almost exclusively the chemical modification of individual nucleotides. In many cases, complexes of snoRNAs and proteins (the snoRNPs) and the related scaRNPs ensure the conversion of uridine to pseudouridine and the 2'-OH methylation of riboses (e.g. in ribosomal RNAs, tRNAs and snRNAs ) - this process is known as RNA modification. However, the direct enzymatic modification of bases without the aid of guide RNAs is far more common . Above all, adenosine deaminases ( English Adenosine Deaminase Acting on RNA , ADAR ) deaminate a large number of adenosine residues in the human transcriptome to inosine (which behaves like guanosine in base pairing) and thus change the information of - according to more recent figures - thousands of transcripts with far-reaching consequences for splicing , RNA stability and translation .

A well-studied example of RNA editing is also the apoB mRNA, in which a tissue-specific ' C to U editing' (deamination) takes place. A stop codon is created in the edited RNA , which leads to a shortened isoform of apolipoprotein B in translation . The responsible catalytic peptide ( APOBEC ) is the most prominent member of the protein family of the same name, which also includes the activation-induced cytidine deaminases (AID). An example of this is the serotonin receptor 5-HT 2C , which can thus adapt its specificity for G proteins and subsequently influence different signal transduction pathways . A large number of brain-specific transcripts are also among the goals of the editing machinery ( potassium channel Kv1.1, glutamate receptor, etc.).

Another important function of RNA editing is the suppression of retrotransposition , especially of aluminum elements, and the defense against RNA viruses including retroviruses (e.g. from HIV RNA) or against DNA viruses with a genomic RNA intermediate ( Pararetroviruses , e.g. the pregenomic RNA of the hepatitis B virus ). The diversity of antibodies is also increased through RNA editing.

RNA editing in plants

Between 20 and 40 nucleotides in the plastids of seed plants do not match their genome - in each of these cases a 'C to U editing' takes place. These changes are much more pronounced in the mitochondria of higher land plants , there is no gene here that is not affected by this modification and the proportion of the changed nucleotides can be up to 20% of the gene. RNA edition does not occur in lower plants ( algae to liverworts ).

Diseases caused by disturbance of RNA editing

Disturbances in the RNA editing apparatus are believed to also contribute to various human diseases. This was suspected, for example, for amyotrophic lateral sclerosis (ALS) and for certain forms of epilepsy , schizophrenia and other neuronal diseases.

Individual evidence

  1. ↑ KD Stuart, A. Schnaufer, NL Ernst, AK Panigrahi: Complex management: RNA editing in trypanosomes. In: Trends Biochem Sci . 30 (2), Feb 2005, pp. 97-105. PMID 15691655 .
  2. ↑ J. Greeve: Inhibition of the synthesis of apolipoprotein B-containing lipoproteins. In: Handb Exp Pharmacol. (170), 2005, pp. 483-517. PMID 16596812 .
  3. ↑ J. Bockaert, S. Claeysen, C. Becamel, A. Dumuis, P. Marin: Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation. In: Cell Tissue Res. 326 (2), 2006, pp. 553-572. PMID 16896947 .
  4. ^ S. Maas, Y. Kawahara, KM Tamburro, K. Nishikura: A-to-I RNA Editing and Human Disease. In: RNA Biol. 3 (1), January 12, 2006, pp. 1-9. PMID 17114938 .