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MicroRNAs as Haematopoiesis Regulators

DOI: 10.1155/2013/695754

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Abstract:

The production of different types of blood cells including their formation, development, and differentiation is collectively known as haematopoiesis. Blood cells are divided into three lineages erythriod (erythrocytes), lymphoid (B and T cells), and myeloid (granulocytes, megakaryocytes, and macrophages). Haematopoiesis is a complex process regulated by several mechanisms including microRNAs (miRNAs). miRNAs are small RNAs which regulate the expression of a number of genes involved in commitment and differentiation of hematopoietic stem cells. Evidence shows that miRNAs play an important role in haematopoiesis; for example, myeloid and erythroid differentiation is blocked by the overexpression of miR-15a. miR-221, miR-222, and miR-24 inhibit the erythropoiesis, whereas miR-150 plays a role in B and T cell differentiation. miR-146 and miR-10a are downregulated in megakaryopoiesis. Aberrant expression of miRNAs was observed in hematological malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myelomas, and B cell lymphomas. In this review we have focused on discussing the role of miRNA in haematopoiesis. 1. Background MicroRNAs (miRNAs) are 20–22 nucleotides long small noncoding RNAs that can bind to the 3′UTR or 5′UTR or in ORF of target mRNA resulting in translational repression or mRNA degradation based on degree of homology. It is believed that miRNAs regulate gene expression in multicellular organisms, but miRNAs are also identified in unicellular algae Chlamydomonas reinhardtii [1]. Interestingly it has been shown that miRNAs can activate the translation. miRNA-122 is specifically expressed in liver where; it plays vital role in fatty acid metabolism and enhances the replication of hepatitis C virus (HCV) RNA by binding to its 5′UTR [2–4]. ?rom et al. found that miR-10a binds to the messenger RNAs (mRNAs) encoding ribosomal proteins to enhance the translation of proteins and ribosomal biogenesis [5]. Due to increase in cloning and computational approaches, there has been a tremendous increase in the number of newly found miRNAs. A total of 9169 miRNAs have been found in different species among which human genome codes for 1424 miRNAs [5]. It has been found that 60% of the human mRNA contains miRNA binding sites. Each mRNA is targeted by many miRNAs conversely and each miRNA can target many mRNAs. miRNAs exhibit different characteristics in plants and mammals. In plants, miRNAs require perfect match with their target mRNAs, whereas in mammals miRNA complementarily covers 2–7 bases, also known as the seed region

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