The Long Non-coding RNAs: Paramount Regulators of the NLRP3 Inflammasome

Abstract

The NOD LRR pyrin domain containing protein 3 (NLRP3) inflammasome is a cytosolic multi-proteins conglomerate with intrinsic ATPase activity. Their predominant presence in the immune cells emphasizes its significant role in immune response. The downstream effector proteins IL-1β and IL-18 are responsible for the biological functions of the NLRP3 inflammasome upon encountering the alarmins and microbial ligands. Although the NLRP3 inflammasome is essential for host defense during infections, uncontrolled activation and overproduction of IL-1β and IL-18 increase the risk of developing autoimmune and metabolic disorders. Emerging evidences suggest the action of lncRNAs in regulating the activity of NLRP3 inflammasome in various disease conditions. The long non-coding RNA (lncRNA) is an emerging field of study and evidence on their regulatory role in various diseases is grabbing attention. Recent studies emphasize the functions of lncRNAs in the fine control of the NLRP3 inflammasome at nuclear and cytoplasmic levels by interfering in chromatin architecture, gene transcription and translation. Recently, lncRNAs are also found to control the activity of various regulators of NLRP3 inflammasome. Understanding the precise role of lncRNA in controlling the activity of NLRP3 inflammasome helps us to design targeted therapies for multiple inflammatory diseases. The present review is a novel attempt to consolidate the substantial role of lncRNAs in the regulation of the NLRP3 inflammasome. A deeper insight on the NLRP3 inflammasome regulation by lncRNAs will help in developing targeted and beneficial therapeutics in the future.

Keywords: NLRP3 inflammasome; chromatin remodeling; cytoplasmic regulation; decoys; lncRNAs; nuclear regulation; scaffolds; transcriptional regulation.