Principal Investigator Harvey Lodish
Erythropoiesis is regulated at multiple levels by different factors to ensure the proper generation of red blood cells in response to various physiological and pathological stimuli. Although the regulation of erythropoiesis by transcription factors and microRNAs is becoming well understood, the modulation of red blood cell development by lncRNAs is still unknown. LncRNAs can regulate gene expression via multiple mechanisms and many lncRNAs are differentially expressed in many developmental and pathological processes, suggesting that they play important biological roles.
Wenqian Hu examined the expression of lncRNAs during erythropoiesis and identified one erythroid-specific lncRNA with potent anti-apoptotic activity. Inhibition of this lncRNA blocks erythroid differentiation and promotes apoptosis. Ectopic expression of this lncRNA prevents erythroid progenitor cells from apoptosis induced by erythropoietin deprivation. This lncRNA represses expression of Pycard, a pro-apoptotic gene, explaining in part the inhibition of programmed cell death. These findings reveal a novel layer of regulation of cell differentiation and apoptosis by a lncRNA. Together with UROP student, Ken Lin, Wenqian is determining the molecular mechanism by which this lncRNA functions, and is performing functional and mechanistic characterization of several additional regulated lncRNAs in erythropoiesis.