Correcting Errors and Creating Diversity: The Vital Roles of RNA Editing

Ribonucleic acid (RNA), often overshadowed by its more famous cousin Deoxyribonucleic acid (DNA), plays a crucial role in the complex dance of life. Beyond its function as a messenger carrying genetic instructions, RNA undergoes a fascinating process called RNA editing, which offers two seemingly contradictory yet critical functions: correcting errors and creating diversity.

Keeping the Code Clean: Error Correction in RNA Editing

During transcription, the process of copying DNA into RNA, errors can occasionally occur. These errors, if not corrected, can lead to the production of malfunctioning proteins, potentially disrupting cellular processes and leading to disease.

One type of RNA editing mechanism employs enzymes called adenosine deaminases acting on RNA (ADARs). These enzymes identify specific sites on double-stranded RNA molecules where a molecule of adenosine (A) has been erroneously incorporated instead of guanosine (G).  They then deaminate the A, converting it to inosine (I), which pairs with cytidine (C) during translation. This process effectively corrects the error in the RNA sequence, ensuring the production of the correct protein.

ADAR Protein

Embracing Change: Creating Diversity with RNA Editing

While error correction is essential for maintaining cellular fidelity, RNA editing also plays a role in introducing controlled diversity within the transcriptome. This diversity can be achieved through various mechanisms, including the insertion, deletion, or substitution of nucleotides within the RNA sequence.

One example of this process occurs in the nervous system, where a specific type of RNA editing called A-to-I editing modifies specific adenosine (A) residues in pre-mRNA molecules of ion channels. This editing event alters the protein sequence, leading to the production of functionally distinct ion channel variants, crucial for the intricate signaling processes in the brain.


Another example of RNA editing creating diversity is seen in trypanosomes, single-celled parasites responsible for sleeping sickness. These organisms utilize a unique form of RNA editing called guide RNA (gRNA)-mediated editing to alter the sequences of their mitochondrial mRNAs. This editing process allows trypanosomes to evade the host immune system and survive within the host cell.

CRISPR-Cas9 mediated gene-editing mechanisms. A single guide RNA (sgRNA) recognizes a genomic region followed by 5'-NGG-3' PAM sequence, which recruits the Cas9 DNA endonuclease. This introduces a double-stranded break that is repaired by (i) non-homologous end joining (NHEJ), an error prone pathway that can result in the creation of Indels that can disrupt the gene, or by (ii) homology directed repair (HDR) in the presence of a donor construct.

The introduction of diversity through RNA editing allows for a single gene to encode multiple protein variants, expanding the functional repertoire of the cell and providing a layer of flexibility in response to different environmental cues.

The Balancing Act: Maintaining Accuracy and Embracing Variation

RNA editing mechanisms operate in a tightly regulated manner. Overediting or under-editing can have detrimental consequences. For instance, excessive A-to-I editing in the nervous system can lead to neurological disorders. Conversely, insufficient editing can prevent the production of essential protein variants, disrupting cellular function.

Understanding the intricate mechanisms and regulation of RNA editing is crucial for deciphering its role in development, health, and disease. Ongoing research is aimed at unraveling the full extent of RNA editing's impact and exploring its potential as a therapeutic target for various conditions.

To learn more about RNA editing, watch this video:

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Correcting Errors and Creating Diversity: The Vital Roles of RNA Editing
Gen store May 20, 2024
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