Palmitic Acid–Induced Long Noncoding RNA PARAIL Regulates Inflammation via Interaction With RNA-Binding Protein ELAVL1 in Monocytes and Macrophages

• DOI: 10.1161/atvbaha.122.318536
• Publication Date: 2023-04-27T09:02:00Z
• Authors: Vinay Singh Tanwar; Marpadga A. Reddy; Sadhan Das; Vishnu Amaram Samara; Maryam Abdollahi; Suchismita Dey; Vajir Malek; Rituparna Ganguly; Kenneth Stapleton; Linda Lanting; Patrick Pirrotte; Rama Natarajan
• Keywords: Inflammation; 0303 health sciences; Macrophages; Palmitic Acid; NF-kappa B; RNA-Binding Proteins; Atherosclerosis; Monocytes; ELAV-Like Protein 1; Mice; 03 medical and health sciences; Humans; Animals; RNA, Long Noncoding

Background: Obesity and diabetes are associated with elevated free fatty acids like palmitic acid (PA), which promote chronic inflammation impaired resolution cardiometabolic disorders. Long noncoding RNAs (lncRNAs) implicated in inflammatory processes; however, their roles PA-regulated unclear. Methods: We performed RNA-sequencing analysis to identify coding genes novel lncRNAs CD14 + monocytes from healthy volunteers. investigated the regulation function of an uncharacterized PA-induced lncRNA PARAIL (PA- r egulated a nti- i nflammatory l ncRNA). examined its role by employing knockdown overexpression strategies human mouse macrophages. also used RNA pulldown coupled mass spectrometry interacting nuclear proteins mechanistic involvement functions Results: Treatment several phenotype. PA strongly induced expressed near RIPK2 . was cytokines infectious agents monocytes/macrophages regulated NF-κB (nuclear factor-kappa B). Time course studies showed during phase PA-treated antisense oligonucleotides upregulated key vice versa overexpression. found that interacts ELAVL1 (ELAV-like RNA-binding protein 1) via adenylate/uridylate–rich elements (AU-rich elements; AREs). inhibited anti-inflammatory Moreover, increased cytosolic localization stability ARE-containing genes. Mouse orthologous Parail downregulated macrophages mice atherosclerosis. attenuated proinflammatory Conclusions: Upregulation under acute conditions contributes proresolution mechanisms -ELAVL1 interactions. Conversely, downregulation diseases enhances impairs further augment inflammation. Thus, inflammation-resolving represent targets combat diseases.