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Archive - Jul 8, 2019

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Scientists Identify an RNA-Binding Protein (SRSF3) As Essential for Correct Heart Contraction & Survival—Capping of Contraction-Related mRNAs Revealed As Key Process Influenced by SRSF3; This Capping Protects Against Development of Systolic Heart Failure

A team of scientists led by Dr. Enrique Lara Pezzi (photo) at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid, Spain, has identified the RNA-binding protein SRSF3 as an essential factor for proper heart contraction and survival. In a study published online on July 5, 2019 in Circulation Research, the researchers found that loss of cardiac expression of SRSF3 leads to a critical reduction in the expression of genes involved in contraction. The new article is titled “Loss of SRSF3 in Cardiomyocytes Leads to Decapping of Contraction-Related mRNAs and Severe Systolic Dysfunction.” Knowledge of the mechanism of action of SRSF3 in the heart could open the way to the design of new therapeutic approaches for the treatment of heart disease. Cardiovascular disease is the leading cause of death in the world. In 2015 alone, cardiovascular disease killed 17.7 million people, with 6.7 million of these deaths caused by heart attack. Unfortunately, knowledge is limited about the molecular mechanisms that regulate progression of a myocardial infarction, sytmying the development of new therapeutic approaches. The recent development of massive-scale mRNA sequencing technology has permitted the identification of gene expression patterns associated with the development of heart disease. Nevertheless, understanding of post-transcriptional regulation (a type of gene regulation) remains limited, in particular about the roles played by RNA-binding proteins (RBPs) in myocardial infarction and the development of heart disease. RNA-binding proteins perform important tasks in the cell. "In this study, we have investigated the role of the RBP SRSF3 in the heart, which was unknown until now," explained Dr. Lara Pezzi. Study first author Dr.

Infection-Fighting Protein (HRI) Also Senses Protein Misfolding In Non-Infected Cells; Finding May Offer Insights into Approaches to Prevent/Treat Neurodegenerative Diseases Like Parkinson’s

Researchers at the University of Toronto in Canada have uncovered an immune mechanism by which host cells combat bacterial infection, and, at the same time, found that a protein crucial to that process can sense and respond to misfolded proteins in all mammalian cells. The protein is called heme-regulated inhibitor (HRI), and the researchers showed that during bacterial infection it triggers and coordinates a chain reaction among other proteins that form a larger complex. That larger group or “signalosome” amplifies inflammation and leads to an anti-bacterial response. But HRI can also regulate protein folding in other cell types, the researchers showed. Protein folding, which helps determine the 3-D shape of a protein and is essential for its function, is implicated in non-infectious diseases including the neurodegenerative disorders Parkinson's, Alzheimer's, and ALS. "The innate immune function that we discovered is essentially a mechanism of protein scaffolding, which is important because you want a quick and orderly response to bacterial infection," says Stephen Girardin (photo), PhD, a Professor of Laboratory Medicine and Pathobiology and of Immunology at th U of Toronto. "But we also found that same pathway is important for protein scaffolding and aggregation in other cells, which opens promising research angles for neurodegenerative and other diseases." The findings were published online in Science nline on July 5, 2019. The article is titled “The Heme-Regulated Inhibitor Is a Cytosolic Sensor Of Protein Misfolding That Controls Innate Immune Signaling.” Researchers have studied HRI for over three decades, but mostly in the context of red blood cell disorders.