Posttranscriptional regulation of erythropoiesis by RNA-binding proteins and microRNAs

Abstract

Humans generate 2.4 million red blood cells every second through a highly dynamic developmental process regulated by multiple hormones. The earliest committed erythroid progenitor BFU-E responds to several hormones, leading to the formation of both additional BFU-Es through partial self-renewal and later Epo-dependent CFU-E progenitors. Epo binds to Epo receptors on the surface of CFU-E progenitors and triggers the formation of mature erythrocytes.

In the first part of my thesis, I identified the RNA binding protein ZFP36l2 as a transcriptional target of the glucocorticoid receptor in the BFU-Es and showed that it is required for BFU-E self-renewal. In the second part of my thesis, I established that the down regulation of microRNA miR-191 is essential for erythroblast chromatin condensation and enucleation by allowing up regulation of two target genes, Riok3 and Mxi1. Together, these results highlight the importance of posttranscriptional regulation in erythropoiesis.