MicroRNAs as regulators and effectors of hematopoietic transcription factors

Abstract

Hematopoiesis is a highly-regulated development process orchestrated by lineagespecific transcription factors that direct the generation of all mature blood cells types, including red blood cells, megakaryocytes, granulocytes, monocytes, and lymphocytes. Under homeostatic conditions, the hematopoietic system of the typical adult generates over 10 11 blood cells daily throughout life. In addition, hematopoiesis must be responsive to acute challenges due to blood loss or infection. MicroRNAs (miRs) cooperate with transcription factors to regulate all aspects of hematopoiesis, including stem cell maintenance, lineage selection, cell expansion, and terminal differentiation. Distinct miR expression patterns are associated with specific hematopoietic lineages and stages of differentiation and functional analyses have elucidated essential roles for miRs in regulating cell transitions, lineage selection, maturation, and function. MiRs function as downstream effectors of hematopoietic transcription factors and as upstream regulators to control transcription factor levels. Multiple miRs have been shown to play essential roles. Regulatory networks comprised of differentially expressed lineage-specific miRs and hematopoietic transcription factors are involved in controlling the quiescence and self-renewal of hematopoietic stem cells as well as proliferation and differentiation of lineage-specific progenitor cells during erythropoiesis, myelopoiesis, and lymphopoiesis. This review focuses on hematopoietic miRs that function as upstream regulators of central hematopoietic transcription factors required for normal hematopoiesis.

Regulation of GATA1 levels in erythropoiesis

“…This interaction reduces the expression levels of GATA1 protein and, consequently, represses hematopoiesis when miR‐152 is overexpressed . In mammals, regulation of GATA‐1 levels by microRNAs has not been validated yet, including miRNAs that have been described to modulate erythropoiesis …”

“…89 In mammals, regulation of GATA-1 levels by microRNAs has not been validated yet, including miRNAs that have been described to modulate erythropoiesis. [90][91][92] 7 | POSTTRANSLATIONAL MODIFICATIONS AND GATA1 PROTEIN STABILITY GATA1 undergoes several posttranslational modifications (PTMs), including phosphorylation, acetylation, sumoylation, and ubiquitination. Phosphorylation occurs in seven serine residues, of which six are constitutively phosphorylated, whereas S310 phosphorylation, located near the C-ZnF of GATA1, is erythroid-specific.…”

Inhibition of microRNA‐148b‐3p alleviates oxygen‐glucose deprivation/reoxygenation‐induced apoptosis and oxidative stress in HT22 hippocampal neuron via reinforcing Sestrin2/Nrf2 signalling

“…The binding of miRNA to mRNA leads to mRNA degradation or translational repression, and thus miRNAs are negative regulators of gene expression . Through the post‐transcriptional regulation of gene expression, miRNAs are believed to regulate various biological processes, including proliferation, apoptosis, the cell cycle, and differentiation, that are involved in both physiological and pathological progress . Currently, accumulating evidence indicates that various miRNAs are dysregulated in cerebral ischaemia/reperfusion injury and can be potentially used as diagnostic and/or therapeutic targets .…”

“…9 Through the post-transcriptional regulation of gene expression, miRNAs are believed to regulate various biological processes, including proliferation, apoptosis, the cell cycle, and differentiation, that are involved in both physiological and pathological progress. [10][11][12] Currently, accumulating evidence indicates that various miRNAs are dysregulated in cerebral ischaemia/ reperfusion injury and can be potentially used as diagnostic and/or therapeutic targets. 13,14 Various studies demonstrated that targeting specific miRNAs can alleviate neuronal injury and recover neurological functions using in vitro and in vivo experimental models of cerebral ischaemia/reperfusion injury.…”

Effect of Beta-Blockade on the Expression of Regulatory MicroRNA after Severe Trauma and Chronic Stress

“…23 MicroRNAs (miRs) are 18 to 24 nucleotide noncoding RNAs that act as epigenetic regulators in biologic processes and have been identified as major regulators of hematopoiesis. [24][25][26][27] These miRs are secreted by a variety of cells through exosomes or protein-mediated pathways. Extracellular miRs are highly stable and not only serve as biomarkers for various diseases, they also act as signaling molecules.…”