The Accornero Lab at Brown University studies RNA Biology in the context of cardiac and skeletal muscle disease.
Welcome to the Accornero Lab!
Publications
Check out some of our recent work below
Loss of YTHDF2 Alters the Expression of m6A-Modified Myzap and Causes Adverse Cardiac Remodeling
JACC Basic to Translational Science
Volha A. Golubeva, Lisa E. Dorn, Christopher J. Gilbert, Charles P Rabolli, Anindhya Sundar Das, Vishmi S. Wanasinghe, Roland Veress, Dmitry Terentyev, Federica Accornero
Abstract
How post-transcriptional regulation of gene expression, such as through N6-methyladenosine (m6A) messenger
RNA methylation, impacts heart function is not well understood. We found that loss of the m6A binding protein
YTHDF2 in cardiomyocytes of adult mice drove cardiac dysfunction. By proteomics, we found myocardial zonula
adherens protein (MYZAP) within the top up-regulated proteins in knockout cardiomyocytes. We further
demonstrated that YTHDF2 binds m6A-modified Myzap messenger RNA and controls its stability. Cardiac
overexpression of MYZAP has been associated with cardiomyopathy. Thus, our findings provide an important
new mechanism for the YTHDF2-dependent regulation of this target and therein its novel role in the maintenance
of cardiac homeostasis.
m6A RNA methylation: A dynamic regulator of cardiac muscle and extracellular matrix
Current Opinion in Physiology
Charles P. Rabolli and Federica Accornero
Abstract
Post-transcriptional modifications encompass a large group of RNA alterations that control gene expression. Methylation of the N6-Adenosine (m6A) of mRNA is a prevalent modification which alters the life cycle of transcripts. The roles that m6A play in regulating cardiac homeostasis and injury response are an active area of investigation, but it is clear that this chemical modification is a critical controller of fibroblast to myofibroblast transition, cardiomyocyte hypertrophy and division, and the structure and function of the extracellular matrix. Here we discuss the latest findings of m6A in cardiac muscle and matrix.
BEX1 is a critical determinant of viral myocarditis
PLOS Pathogens
Coltons R. Martens, Lisa E. Dorn, Adam D. Kenney, Shyam S. Bansal, Jacob S. Young, Federica Accornero
Abstract
Viral infection of the heart is a common but underappreciated cause of heart failure. Viruses can cause direct cardiac damage by lysing infected cardiomyocytes. Inflammatory immune responses that limit viral replication can also indirectly cause damage during infection, making regulatory factors that fine-tune these responses particularly important. Identifying and understanding these factors that regulate cardiac immune responses during infection will be essential for developing targeted treatments for virus-associated heart failure. Our laboratory has discovered Brain Expressed X-linked protein 1 (BEX1) as a novel stress-regulated pro-inflammatory factor in the heart. Here we report that BEX1 plays a cardioprotective role in the heart during viral infection. Specifically, we adopted genetic gain- and loss-of-function strategies to modulate BEX1 expression in the heart in the context of coxsackievirus B3 (CVB3)-induced cardiomyopathy and found that BEX1 limits viral replication in cardiomyocytes. Interestingly, despite the greater viral load observed in mice lacking BEX1, inflammatory immune cell recruitment in the mouse heart was profoundly impaired in the absence of BEX1. Overall, the absence of BEX1 accelerated CVB3-driven heart failure and pathologic heart remodeling. This result suggests that limiting inflammatory cell recruitment has detrimental consequences for the heart during viral infections. Conversely, transgenic mice overexpressing BEX1 in cardiomyocytes revealed the efficacy of BEX1 for counteracting viral replication in the heart in vivo. We also found that BEX1 retains its antiviral role in isolated cells. Indeed, BEX1 was necessary and sufficient to counteract viral replication in both isolated primary cardiomyocytes and mouse embryonic fibroblasts suggesting a broader applicability of BEX1 as antiviral agent that extended to viruses other than CVB3, including Influenza A and Sendai virus. Mechanistically, BEX1 regulated interferon beta (IFN-β) expression in infected cells. Overall, our study suggests a multifaceted role of BEX1 in the cardiac antiviral immune response.