%0 Journal Article
%T The Role of Translation Initiation Regulation in Haematopoiesis
%A Godfrey Grech
%A Marieke von Lindern
%J International Journal of Genomics
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/576540
%X Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control. 1. Introduction Hematopoietic stem cells (HSCs) have a life-long capacity to replenish the stem cell compartment and give rise to multipotent progenitors. These progenitors expand to maintain the hematopoietic compartment and differentiate into various blood lineage progenitors. Lineage positive progenitors are committed for differentiation into mature blood cells. Transcription factors have a pivotal role in hematopoiesis to maintain a gene expression program that endows self-renewal properties to HSCs and enables commitment and differentiation into different blood cell lineages [1]. The upregulation of both PU.1 and Gata-1 reprograms HSC to become common myeloid progenitors (CMPs) [2]. The CMPs undergo further lineage divergence into megakaryocyte/erythroid progenitors (MEPs) and granulocyte/monocyte progenitors (GMPs) upon Gata-1 and PU.1 mutual exclusive expression, respectively. Commitment to the erythroid lineage is characterized by the expression of erythroid-specific transcription factors Gata-1, Eklf, and Nfe2 determining the erythroid program. Upon commitment, the balance between proliferation and differentiation of lineage-specific progenitors is under tight control, to maintain the progenitor pool and ensure maturation in response to physiological demand. The production of increased numbers of mature blood cells during stress situations such as inflammation or hypoxia requires higher progenitor
%U http://www.hindawi.com/journals/ijg/2012/576540/