What are regulatory RNAs?

If all cells in an organism carry the same genome, which is encoded in DNA, how can we have so many different tissues and organs, such as neurons, heart, skin, and eyes? Our DNA is like the control center of the cells that build related molecules of RNA to be decoded into proteins. Proteins are the building blocks of cells and carry out jobs in the cells for them to function.

The pieces of DNA that create proteins are called genes. Humans have about 20.000 genes and more than half still have unknown functions. In fact, only 2% of our genes trigger the production of proteins, while the vast majority is expressed, that is, produce RNA, but not necessarily guide the production of proteins. These genes are called non-coding genes and the RNA they produce are called non-coding RNA, also known as regulatory RNA.

RNA molecules come in different sizes and types and can play many important functions in the cells. Non-coding RNA is one of such types, for which a major role is regulating how genes are expressed, that is, how they are turned on and off. Non-coding RNAs comprise a heterogeneous group of both short and long RNAs. So far, the most studied class is a very small RNA molecule, called microRNA (miRNA), followed by its longer cousin, long non-coding RNA (lncRNA).

Thousands of regulatory RNAs, both small and long, have been found in humans, but the role of many of them, especially the long, is still obscure.

Cardiovascular disease and regulatory RNAs

Regulatory RNAs can be found in different organs as well as circulating in the blood. Furthermore, they may be expressed in a very specific manner, particularly in relation to disease states. For example, some are enriched in the heart, others in the brain, while others in the liver. Several regulatory RNAs are dysregulated in many diseases. Such specificity suggests they play an important role in regulating gene expression and may shed light to treat these diseases.

In the last few years, different studies have demonstrated the importance of regulatory RNAs for cardiac development and cell differentiation and several have been implicated in cardiovascular diseases.

We are just beginning to understand how regulatory RNAs influence cardiovascular disease, where they have dysregulated expression in heart failure, hypertension and coronary artery disease (CAD), including atherosclerosis and myocardial infarction. Such changes in expression have been shown in both humans and rodent models, with some studies presenting encouraging results for disease prognosis and therapy.


Author: Clarissa Pedrosa da C. Gomes