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Top Things to Know:
Noncoding RNAs in Cardiovascular Disease

  1. This scientific statement reviews the existing literature on noncoding RNAs, offers guidance on tools and technologies currently available to study noncoding RNAs, and identifies areas of unmet need.
  2. The noncoding RNA landscape, including small RNAs (miRNAs, sno/snRNAs, tRNA fragments, YRNA fragments and piRNAs) and longer noncoding RNAs (including lncRNAs, circRNAs), have been profiled in tissue, biofluids, and even at the level of single cells in the context of cardiovascular diseases.
  3. The use of deep RNA sequencing (RNA-seq) in tissue and biofluids has revealed the noncoding transcriptome in unprecedented detail and created the need to develop better computational and experimental tools to understand their functions.
  4. Modern genetic approaches to effect gain and loss of function for noncoding RNAs continue to be developed and include genetic (CRISPR-based genome editing) and pharmacological tools (such as gapmer-based methods for lncRNAs and locked nucleic acid antagomirs for miRNAs).
  5. Noncoding RNAs have also been found in biofluids, associated with different types of carriers, including extracellular vesicles. This has led to investigation of their role as disease biomarkers that may identify patient subpopulations or allow for monitoring of disease trajectory.
  6. Investigation of long noncoding RNAs and circular RNA function has revealed complex, diverse roles in cardiac development and disease pathogenesis, including epigenetic regulation, function as micropeptides, and regulation of small RNAs.
  7. MiRNAs can serve as key regulators of molecular networks in cardiac development, cardiac physiology, and cardiac disease pathogenesis by targeting mRNAs for post-transcriptional repression through recognition of mRNA target sequences by seed sequences present on the miRNAs.
  8. Emerging work with small noncoding RNAs outside of miRNAs (snoRNAs, piRNAs, YRNA and tRNAs fragments) is beginning to suggest central roles in cardiac, vascular and metabolic disease pathogenesis, although tools to manipulate these sub-types are still early in development.
  9. The investigation of noncoding RNAs has exponentially expanded, leading to new knowledge about the function of RNA molecules and insight into their role as therapeutic targets of biomarkers.
  10. The use of novel RNA epigenetic biomarkers and the targeting of pathways regulated by noncoding RNAs are poised to make a significant impact in cardiovascular disease and health in the next decade.

Citation

Das S, Shah R, Dimmeler S, Freedman JE, Holley C, Lee J-M, Moore K, Musunuru K, Wang D-Z, Xiao J, Yin K-J; on behalf of the American Heart Association Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Noncoding RNAs in cardiovascular disease: current knowledge, tools, and technologies for investigation, and future directions: a scientific statement from the American Heart Association. Circ Genom Precis Med. 2020;13:e000062. doi: 10.1161/HCG.0000000000000062