PU.1-induced regulator of alarmin transcription (PIRAT)

PIRAT (PU.1-induced regulator of alarmin transcription) is a nuclear long intergenic non-coding RNA (lincRNA) expressed primarily in human myeloid cells, notably CD14+ monocytes[1][2]. It acts as a negative feedback regulator of the transcription factor PU.1, retaining it at pseudogene loci and preventing its binding at the promoters of the inflammatory alarmins S100A8 and S100A9, thereby limiting excessive alarmin production during systemic immune responses such as those occurring in severe COVID-19[1][2]. PIRAT regulation is dynamic; it is downregulated via NF-κB signaling during acute immune activation, which unleashes increased production of S100A8/A9 and contributes to inflammatory pathology. Sequence conservation is high in primates but low in rodents, and its overall coding potential is extremely low, confirming its role as a non-protein-coding RNA. Disruption of PIRAT does not appear to be directly disease-causing, but variations (such as SNPs) in its locus have been linked to hematological malignancies and altered platelet volume[1][2].

Other names

PIRATLINC00211NCRNA00211PU.1-induced regulator of S100A8 and S100A9 alarmin transcription 1Long intergenic non-protein coding RNA 211PIRAT1

No direct therapeutic targeting mechanism known.