Could long non-coding RNA foster cardiovascular diseases?

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Recent studies have revealed that the non-coding genome plays a vital role in gene regulation and genetic programming, during the phases of development, along with health and cardiovascular ailments.  Nearly 99% of the genome in the human body do not take part in protein-encoding, however, they all are active in the representation of a broad spectrum of non-coding RNAs. This has important structural and regulatory functions. The non-coding RNAs have been declared as novel regulators of the risk factor of cardiovascular diseases and important cell functions. These are also important candidates that are utilized for the improvement of the prognosis and diagnosis assessment.   

On the initial level, the RNAs provide the therapeutic and novel targets, some of which enter the clinical assessment.  On the second level, the tools for new therapy were developed out of the endogenous ncRNA, which serves as blueprints. The particular advancement is in the development of RNA interference drugs, which have recently been discovered. The interfering RNAs are becoming versatile to efficiently silence the protein expression.
 

The pioneering of the clinical studies includes the drug targeting of RNA in the liver synthesis of PCSK9. This result is a significant lowering of LDL cholesterol or targeting liver transthyretin synthesis for the treatment of cardiac amyloidosis. Moreover, the novel drugs mimic the actions of endogenous ncRNA that arises from the exploitation of molecules that are inaccessible to traditional pharmacology.  Researchers can now give an update on the recent developments and the perspective related to therapeutic and diagnostic uses of ncRNAs in cardiovascular diseases, including coronary disease, heart failure, post-myocardial infarction remodeling. 

The discovery of non-protein-coding RNA

After discovering that most non-protein-coding genes are transcribed and they play a crucial role in the fundamental cellular process, the way has been paved for a plethora of development tools and technologies for the investigation of the role of the noncoding RNAs to treat cardiovascular health and for targeted therapy.

The major role of non-coding RNAs in disease and Health

Although most of the human genome does not take part in encoding proteins, the proteins have been observed to be transcriptionally active and they are thought to give rise to a wide spectrum of ncRNAs with the regulation on structural functions. A steep increasing fraction is observed of non-coding RNAs, which is in contrast to the modest increase of protein-coding genes during the evolution period from a simple single-celled organism to complex humans.

The ncRNAs, like microRNAs -which are respectively small interference RNAs and long non-coding RNAs, are novel regulators of risk factors in cardiovascular diseases and the assessment of the prognosis.

Non-coding RNA has now broadened the spectrum of therapeutic options regarding pathogenesis, which has become apparent from the Encyclopedia of DNA Elements and other studies. The limiting analysis to protein-coding regions of the human genome is not adequate, since a lot of non-coding variants have associations with serious human illnesses.

There is an inclusion of non-coding genomic elements in the study of pathogens that seem to be mandatory and the comprehensive mapping of transcriptome includes all small and large ncRNAs with the addition of genes that code proteins. miRs in the heart regulate post-transcriptional gene expression and it has been proved to monitor the development of cardiovascular inflammation, regeneration, hypertrophy, inflammation, and fibrosis.

The role of non-coding RNA as tools for therapy and diagnosis

Other than offering prognostic and diagnostic biomarkers, non-coding RNA can also be tools or targets for novel strategies of therapy. Therefore, RNA interference and siRNAs are considered extremely versatile and purposeful tools, for instance, they are used to silence the protein-encoding gene through targeting messenger RNA. Dr. Fire and Dr. Mello were awarded the Nobel prize of physiology in 2006 for unearthing RNA interference, i.e. gene silencing through double-stranded RNA. This rapidly explored a novel therapeutic principle for cardiovascular ailments. There have been several studies that have demonstrated the therapeutic potential of organs targeting RNA based on the viral vectors and therapeutic strategies on the basis of modulation of miRs. An increasing spectrum of endogenous non-coding RNA is employed for the maturation of novel therapeutic non-coding RNA tools. These are optimized for certain therapeutic requirements.  (Poller, 2018)

Results of the study 

There has been significant progress in the initial studies that focus on the role of microRNAs in the development of cardiovascular development and disease. It has been noted recently that the progress on understanding the role of novel types of non-coding small RNAs, like fragments of transcription RNA, small nucleolar RNA, transfer RNA, and Y-RNAs in the cellular process has revealed non-canonical functions for most of these molecules. The same is the case with the identification of long non-coding RNAs that play an imperative role in the process of cardiovascular diseases. This is coupled with the production of tools that characterize the unique role of extracellular RNAs mediating intercellular communication and their role as potential biomarkers.

Conclusion

The sudden expansion of pipelines and tools for measuring, isolating, and annotating these entities offer a suggestion of being cautious to interpret the warranted results unless the methodologies like these are rigorously validated. 

Many investigators are focused on the investigation of the functional role of separate RNA entities, but the studies also suggest that there is a complex interaction between the different RNA molecules. The approach of network and advanced computational appliances is needed to evaluate the interaction between various noncoding RNAs to mediate a certain phenotype. This requires completely comprehending the functionality of non-coding RNAs in mediation phenotype disease.

Most of the non-protein-coding genome was earlier believed to be non-functional. That’s why this notion had led to a revolution in biology. Over the past several decades, the understanding of how non-coding RNAs contribute significantly to normal homeostasis and pathogenesis. It has exponentially highlighted the novel classes of RNA molecules. Although the microRNAs have mostly been studied in the development of cardiovascular development and disease. The incoming investigation has started to include other types of sncRNA species. (Das, 2020)

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References

Poller, Wolfgang, et al. “Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives.” European Heart Journal, vol. 39, no. 29, 2018, pp. 2704–2716. PMS US National Library of Medicine National Institutes of Health, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454570/.

Das, Saumya, et al. “Noncoding RNAs in Cardiovascular Disease: Current Knowledge, Tools and Technologies for Investigation, and Future Directions: A Scientific Statement From the American Heart Association.” Genomic and Precision Medicine, Jun, https://www.ahajournals.org/doi/full/10.1161/HCG.0000000000000062?af=R. Accessed 29 Jun 2020.

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