RNA editing – EXPLAINED!

Imagine being able to know the biological cause of complex and multifactorial diseases such as depression, schizophrenia, non-hereditary cancer and so on, with a simple blood or tissue sample. Imagine that scientific community discovers new drug targets thanks to this new knowledge. Imagine that each of us can access personalized medicine.

Utopia or new frontier of medicine? 

This is the current challenge of molecular biology and modern medicine. The development of new diagnostic techniques and Next Generation Sequencing (#NGS) has allowed scientists to learn more about the biological of disease and has led to the rewriting of many hypotheses.

How it all started 

The "one gene-one enzyme" paradigm, postulated by Beadle in 1945, states that each gene leads to the production of a single protein product. Today, thanks to the discovery of the changes that occur during the decoding and production of proteins, scientists know that each gene could lead to the production of different proteins in terms of biological function and disease progression.

As molecular biology teaches, a single gene, present in our #DNA, enzymatically transfers the rules and structure information to build a protein using #RNA. Subsequently, the RNA will be read by specific cellular components to build the final protein. Imagine the whole process like baking your favorite cake. DNA is the recipe; RNA is the way by which the recipe becomes a cake.

Modifications of RNA influence its function and stability and the modern molecular techniques (NGS, #RNASequencing and similar) allowed the discovery of more than 100 distinct types of RNA modifications, whose functions are largely unknown. Though, their presence in many species point towards their evolutionarily importance and their role in global genome evolution through individual adaptation. The composition and complexity of the total set of RNAs expressed into a single cell, tissue, or organism (the transcriptome) are believed to account for the increased cellular and functional sophistication of plants, animals and humans and are determined in part by RNA modifications.

RNA Editing

One of the most studied modifications is the co-transcriptional event of “RNA editing”, a unique and fascinating process that can alter the cellular fate of RNA molecules, through the alteration of the proteins’ primary structure (by introducing single amino acid substitutions, new start and stop codons or by modifying splicing sites), and their stability. The most common type is A to I editing, in which a specific group of enzymes (#ADAR) are responsible for transforming one building block of RNA into another. In fact, they replace adenosine with inosine and lead to the production of a different protein. Imagine that, while cooking, you accidentally change the recipe, add salt to the dough instead of sugar. So, you could potentially get pizza instead of cinnamon rolls or give you a tummy ache. Likewise, ADAR enzymes lead to proteins with different roles within cells and organisms, even with pathological consequences.

Just as RNA editing events might act like genomic mutations to drive adaptation, deregulated RNA editing might have effects like disease-related genomic mutations. These aberrant editing events could be viewed as a new class of non-heritable RNA mutation, detectable through NGS, under certain conditions, at a specific stage of a disease or in certain cells or tissues.

RNA Editing and Precision Medicine

In the “Era of #PrecisionMedicine”, the combination of epigenetic data with blood-based biomarkers, behavior and clinical factors can lead to identify disease-specific biological aspects that help to stratify disease, allocate patient subgroups to specific treatment options, and to identify subjects at risk or within a prodromal state. In this way precision medicine provides, or is going to offer, specific treatment options and preventive strategies tailored to the individual person.

According to this, aberrant RNA editing has been already correlated with several different human disorders, including amyotrophic lateral sclerosis, epilepsy, depression-related suicide, schizophrenia, and bipolar disorder. Recently developed computational and experimental approaches are already being used to screen for altered editing in neurological and brain disorders, and initial results show its occurrence in the central nervous system after injuries, Alzheimer disease and autism. Indeed, all the editing-induced dynamics in the transcriptome are essentials for normal brain development, and scientific community is only beginning to understand its role in neuronal function. Furthermore, A-to-I editing, expanding the functional output of many important neuronally expressed genes, could be a target for the development of Precision Psychiatry molecular tests.  

As a matter of fact, NGS technologies in combination with accurate bioinformatic pipelines made possible the detection of thousands of new RNA editing sites and could be pivotal in revealing new or hidden RNA editing events. Scientists and physicians expect that advances in editing screening technologies will help to reveal more associations between the pathological effects observed in a variety of disorders and RNA mutations. The emergent attention to this field is leading to a deeper understanding of the molecular mechanisms and aberrations linked to specific medical conditions and future perspectives include not only neurological and psychiatric conditions, but also cancer and cardiovascular diseases. 

Growing evidence suggests that the levels of RNA editing, along with the expression of specific enzymes, tumor suppressor genes and oncogenes, could be used as important prognostic biomarkers in cancer pathogenesis and progression. The molecular analysis of these specific markers between tumor and normal tissues, as well as within cancer types, revealed a promising scheme of clinical value towards a better understanding of cancer development and its corresponding treatment.

 Conclusion

RNA editing screening opens new perspectives for precision medicine, especially in the psychiatric field. The mammalian brain requires a precise developmental program that drives complex connections between billions of neurons, many data support a role for #RNAediting as a dynamic regulator of many of the key molecules controlling neuronal function. Therefore, it is of great importance to expand the current knowledge.

A new frontier of medicine is about to be reached and a deeper understanding of RNA editing along with personalized medicine will make utopia come true.

#EditB #mentalhealth #mentalhealthawareness #precisionpsychiatry