Noncoding RNAs and Stroke

Acknowledgments

This work was supported by NIH grant NS079585, VA merit review grant 1I01BX002985, and American Heart Association grant 15IRG23050015.

Introduction

Stroke (cerebral ischemia)-induced brain damage is a complex injury that begins with loss of oxygen and nutrient flow to the brain due to blockage of one or more cerebral arteries by plaque formation leading to embolism. This acute shortage of essential elements triggers a plethora of molecular events that ultimately result in widespread inflammation, oxidative stress, edema, apoptotic and necrotic cell death, and ultimately scarring of the tissue. This in turn results in loss of function in the affected regions that induces serious disabilities in the stroke survivors. Although the molecular and cellular mechanisms underlying the progression of ischemic pathophysiology have been well studied, a majority of the studies were focused on proteins and protein-coding genes. Advances in the discovery and characterization of various classes of noncoding RNAs (ncRNAs) revealed a novel layer of regulatory mechanisms that is important for the modulation of transcription and translation, and normal cellular physiology. In this chapter, we discuss the studies that evaluated the significance of ncRNAs in promoting brain damage and/or plasticity after stroke.

Noncoding RNAs

Early studies on the mechanisms of polypeptide synthesis identified two distinct types of RNAs within the translational machinery that did not encode peptides. These include the ribosomal RNAs (rRNA), which interact with a variety of proteins to form ribonucleoprotein complexes that catalyze peptide bond formation to assemble amino acids into polypeptide chains, and the transfer RNAs (tRNAs), which recognize, bind, and transport individual amino acids to the rRNA complexes to be incorporated into the growing polypeptide chains. Together, these two classes of ncRNAs are indispensable to protein translation. Over the past 20 years, many studies including the Human Genome Project and the Encyclopedia of DNA Elements (ENCODE) indicated that the majority of the RNAs transcribed by the mammalian genome are ncRNAs. To date, 20 subtypes of ncRNAs have been conclusively identified that differ from each other in their biogenesis, size, subcellular localization, and function . The three subtypes that have been studied widely in the mammalian brain are microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and long noncoding RNAs (lncRNAs).

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here