microRNAs: fine tuning of erythropoiesis

Abstract

Cell proliferation and differentiation is a complex process involving many cellular mechanisms. One of the best-studied phenomena in cell differentiation is erythrocyte development during hematopoiesis in vertebrates. In recent years, a new class of small, endogenous, non-coding RNAs called microRNAs (miRNAs) emerged as important regulators of gene expression at the post-transcriptional level. Thousands of miRNAs have been identified in various organisms, including protozoa, fungi, bacteria and viruses, proving that the regulatory miRNA pathway is conserved in evolution. There are many examples of miRNA-mediated regulation of gene expression in the processes of cell proliferation, differentiation and apoptosis, and in cancer genesis. Many of the collected data clearly show the dependence of the proteome of a cell on the qualitative and quantitative composition of endogenous miRNAs. Numerous specific miRNAs are present in the hematopoietic erythroid line. This review attempts to summarize the state of knowledge on the role of miRNAs in the regulation of different stages of erythropoiesis. Original experimental data and results obtained with bioinformatics tools were combined to elucidate the currently known regulatory network of miRNAs that guide the process of differentiation of red blood cells.Electronic Supplementary MaterialSupplementary material is available for this article at 10.2478/s11658-012-0038-z and is accessible for authorized users.

miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2

“…Nonetheless, the implication of Nrf2-regulated miRNAs in anti-stress machinery is largely undefined. Mounting data demonstrate that miRNAs play important roles in directing erythropoiesis [31,33]. For instance, mice with deficiency of miR-144 and miR-451 showed such pronounced phenotypes as impaired late erythrocyte maturation, causing anemia and erythroid hyperplasia coupled to splenomegaly [65].…”

“…Accumulating evidences suggested that miRNAs contribute to regulating erythropoiesis, and a few miRNAs are involved in erythropoiesis including proliferation of erythroid precursors, fetal γ-globin expression and enucleation [31][32][33][34]. It was also reported that miR-451 targeted 14-3-3zeta to activate FoxO3 pathway to protect erythroid cells from oxidant stress [35].…”

MicroRNA Dysregulation Associated with Red Blood Cell Storage

“…miRNA-96 is known for its abundance in adult blood reticulocytes, where it decreases γ-globin expression typical of fetal hemoglobin (α2γ2) allowing for the predominance of adult hemoglobin (α2β2) when reticulocytes mature into erythrocytes [32,33]. As a consequence of that, miRNA-96 silencing induces an increase in γ-globin [32,33].…”

“…As a consequence of that, miRNA-96 silencing induces an increase in γ-globin [32,33]. In addition, overexpression of miRNA-96-5p inhibits autophagy and apoptosis in human breast cancer cells [34].…”

Regulation of the unfolded protein response by microRNAs

“…However, some more recent studies suggest that the latter is the more common mechanism for miRNA regulation [41]. They have been linked to a number of cellular processes, including apoptosis [42], inflammatory responses [43] and erythropoesis [44]. However, we are just beginning to understand their impact on cellular stress responses, such as hypoxia [45,46], oxidative stress [47,48], and various types of UPR activation, including insulin secretion [49] and B-cell differentiation [50].…”