Long Non-coding RNA Aerrie Controls DNA Damage Repair via YBX1 to Maintain Endothelial Cell Function

Abstract

Aging is accompanied by many physiological changes. These changes can progressively lead to many types of cardiovascular diseases. During this process blood vessels lose their ability to maintain vascular homeostasis, ultimately resulting in hypertension, stroke, or myocardial infarction. Increase in DNA damage is one of the hallmarks of aging and can be repaired by the DNA signaling and repair system. In our study we show that long non-coding RNA Aerrie (linc01013) contributes to the DNA signaling and repair mechanism. Silencing of Aerrie in endothelial cells impairs angiogenesis, migration, and barrier function. Aerrie associates with YBX1 and together they act as important factors in DNA damage signaling and repair. This study identifies Aerrie as a novel factor in genomic stability and as a binding partner of YBX1 in responding to DNA damage.

Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding RNA Targets, Challenges and Therapeutic Opportunities

“…Linc01013 is also known as Age and EndMT regulated RNA in endothelium (Aerrie) ( Pham et al, 2020 ). The function of linc01013 is poorly characterized.…”

“…The function of linc01013 is poorly characterized. Recently, it was revealed that its expression was induced by oscillatory flow and aging in HUVECs, and induced in atherosclerotic plaques from symptomatic patients compared to asymptomatic patients and in ischemic heart tissues from the left ventricle ( Pham et al, 2020 ). Loss of Aerrie impaired cellular migration, barrier function, and angiogenic sprouting of HUVECs ( Pham et al, 2020 ).…”

“…Recently, it was revealed that its expression was induced by oscillatory flow and aging in HUVECs, and induced in atherosclerotic plaques from symptomatic patients compared to asymptomatic patients and in ischemic heart tissues from the left ventricle ( Pham et al, 2020 ). Loss of Aerrie impaired cellular migration, barrier function, and angiogenic sprouting of HUVECs ( Pham et al, 2020 ). Aerrie interacts with Y-Box protein 1 (YBX1), a protein involved in stress response and DNA repair among other functions in mammalian cells ( Pham et al, 2020 ).…”

“…Loss of Aerrie impaired cellular migration, barrier function, and angiogenic sprouting of HUVECs ( Pham et al, 2020 ). Aerrie interacts with Y-Box protein 1 (YBX1), a protein involved in stress response and DNA repair among other functions in mammalian cells ( Pham et al, 2020 ). Loss of Aerrie leads to DNA damage and activated DNA damage signaling ( Pham et al, 2020 ).…”

“…Aerrie interacts with Y-Box protein 1 (YBX1), a protein involved in stress response and DNA repair among other functions in mammalian cells ( Pham et al, 2020 ). Loss of Aerrie leads to DNA damage and activated DNA damage signaling ( Pham et al, 2020 ). Silencing YBX1 rescued DNA damage signaling activated by the loss of Aerrie without any effects on DNA damage itself ( Pham et al, 2020 ).…”