MicroRNAs in Benign and Malignant Hematopoiesis

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					                                                      Resident Short Review

       MicroRNAs in Benign and Malignant Hematopoiesis
                                    Sharathkumar Bhagavathi, MD; Magdalena Czader, MD, PhD

N MicroRNAs (miRNAs) arethat regulate of 19- to RNA
nucleotide noncoding RNAs
                           a family
                                                 24-                   does not code a protein but produces a pair of small
                                                                       RNAs, which negatively regulates the lin-14 translation
function at the posttranscriptional and translational level.           via an antisense RNA-RNA interaction. Subsequent
Recent literature demonstrates a significant role of                   reports on miRNAs underscored the vital role of miRNAs
miRNAs in normal and malignant hematopoiesis. Specific                 in regulating gene expression through RNA-RNA inter-
miRNAs have been shown to regulate each step of                        actions. In 2000, Reinhart and colleagues2 discovered
hematopoiesis starting at the level of multipotent progen-             another regulatory gene in Caenorhabditis elegans, let-7,
itors through terminal stages of myeloid and lymphoid                  which was also involved in the timing of nematode
differentiation. Similarly, individual miRNAs and miRNA                development. The term miRNA was introduced in 2001.3
signatures have been associated with specific hematologic              The inertia about appreciating the role of miRNAs was
malignancies. There is accumulating evidence that miRNAs               partly due to the understanding that miRNAs play a
can be used for diagnostic, prognostic, and therapeutic                critical role in regulation of the life cycle of worms.
purposes. This review highlights the current status of                 However, in 2001, miRNAs were identified and cloned in
knowledge on miRNA in normal and malignant hemato-                     various animal species including fish, birds, and mam-
poiesis.                                                               mals. It also became clear that miRNA sequences are
   (Arch Pathol Lab Med. 2010;134:1276–1281)                           phylogenetically conserved during evolution and most
                                                                       mRNAs are posttranscriptionally regulated by miRNAs.
                                                                       The human genome encodes at least 1000 miRNAs, which
The discovery MicroRNAs are ofa normal ofsignificantly
               of microRNA (miRNA) has
   improved our understanding
                                       and abnormal
                                                                       are located in all chromosomes except chromosome Y
                                                                       implying their potential in influencing various pathways
RNAs that play an important role in development of                     in cellular proliferation, differentiation, and apoptosis.
plants and invertebrates and vertebrate animals. It is
believed that miRNAs are modulators of messenger RNA
(mRNA) translation and stability, although most target                   MicroRNAs are derived from primary miRNAs, which
mRNAs remain to be identified. This review discusses the               are transcribed by RNA polymerase II with a cap and
current understanding of miRNAs and their role in                      poly A tail (Figure 1). The primary miRNAs are cleaved
hematopoiesis and in hematologic malignancies.                         by ribonuclease III Drosha and the double-stranded
                                                                       DNA binding protein Pasha/DGCR8 into a 70- to 100-
                 DEFINITION OF miRNA                                   nucleotide stem loop structure pre-miRNAs, which are
  MicroRNAs are a family of 19- to 24-nucleotide                       exported to the cytoplasm by exportin 5/Ran GTP.
noncoding RNAs that regulate stability and translation                 Subsequently, Dicer ribonuclease III processes pre-
of mRNA by 
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