%0 Journal Article
%T MicroRNAs in Acute Myeloid Leukemia and Other Blood Disorders
%A Yao Yuan
%A Siddha Kasar
%A Chingiz Underbayev
%A Sindhuri Prakash
%A Elizabeth Raveche
%J Leukemia Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/603830
%X Common blood disorders include hematopoietic cell malignancies or leukemias and plasma cell dyscrasia, all of which have associated microRNA abnormalities. In this paper, we discuss several leukemias including acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) and identify altered microRNAs and their targets. Immune disorders with altered blood levels of antibodies include autoimmune disorders, such as systemic lupus erythematosus (SLE) with associated anti-self-autoantibodies and immunoglobulin A nephropathy (IgAN) also have related microRNA abnormalities. The alterations in microRNAs may serve as therapeutic targets in these blood disorders. 1. Introduction MicroRNAs are small (20每22ˋnt), evolutionarily conserved, noncoding single-stranded RNAs discovered in the 1990s [1, 2], functioning to target 3∩ untranslated region (UTR) of mRNAs in antisense sequence specific way and regulate genes posttranscriptionally for degradation or translation suppression. MicroRNAs target 1每3% of all eukaryotic genes yet regulating ~30% of protein-coding genes [3]. The miRNAs are first transcribed by RNA polymerase II in the nucleus as large primary transcript (pri-miRNA) [4], either from independent genes or from clustered genes encoding several miRNAs [5] and further processed into ~70ˋnt pre-miRNA with hairpin structure by Drosha, a RNase III type endonuclease (RN3) in the nucleus. Alternatively, in the nucleus, a small class of ※mintron§ without the stem-loop and the flanking single-strand structure as in pri-miRNA required for Drosha processing, could be generated by passing Drosha-dependent pathway [6]. In the cytoplasm, ~20ˋbp miRNA/miRNA* duplex are generated by Dicer, another RN3 endonuclease. One of the miRNA duplex strands is further incorporated into protein-RNA complex called RNA-induced silencing complex (RISC), although in some cases, both arms of the pre-miRNA hairpin could generate mature miRNAs [7每9]. miRNAs interact with target mRNA by sequence complementarity, and in perfect base pairing usually triggers endonucleolytic mRNA cleavage [10]; however, in most situations, such base pairing is imperfect, resulting in translational suppression. The key component of this RISC machinery is Ago protein family (Ago 1每4), but only Ago 2 is known to have the catalytic enzyme function [11, 12]. Besides Ago proteins, GW182 protein is also recruited to the RISC complex and together localize in cytoplasmic foci called processing bodies (P bodies or GW bodies), where mRNA is sequestered from being translated [13每16]. There are different experimental
%U http://www.hindawi.com/journals/lrt/2012/603830/