title: AU-rich RNA binding proteins in hematopoiesis and leukemogenesis.
abstract: Posttranscriptional mechanisms are now widely acknowledged to play a central role in orchestrating gene-regulatory networks in hematopoietic cell growth, differentiation, and tumorigenesis. Although much attention has focused on microRNAs as regulators of mRNA stability/translation, recent data have highlighted the role of several diverse classes of AU-rich RNA-binding protein in the regulation of mRNA decay/stabilization. AU-rich elements are found in the 3'-untranslated region of many mRNAs that encode regulators of cell growth and survival, such as cytokines and onco/tumor-suppressor proteins. These are targeted by a burgeoning number of different RNA-binding proteins. Three distinct types of AU-rich RNA binding protein (ARE poly-U-binding degradation factor-1/AUF1, Hu antigen/HuR/HuA/ELAVL1, and the tristetraprolin/ZFP36 family of proteins) are essential for normal hematopoiesis. Together with 2 further AU-rich RNA-binding proteins, nucleolin and KHSRP/KSRP, the functions of these proteins are intimately associated with pathways that are dysregulated in various hematopoietic malignancies. Significantly, all of these AU-rich RNA-binding proteins function via an interconnected network that is integrated with microRNA functions. Studies of these diverse types of RNA binding protein are providing novel insight into gene-regulatory mechanisms in hematopoiesis in addition to offering new opportunities for developing mechanism-based targeted therapeutics in leukemia and lymphoma.
authors.affiliation: Department of Biological Sciences, University of Essex, Colchester, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Baou
authors.forename: John D
authors.initials: JD
authors.lastname: Norton
authors.forename: John J
authors.initials: JJ
authors.lastname: Murphy
mesh_terms: D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D053263:Gene Regulatory Networks / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics*; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D051959:ELAV Proteins; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C105789:KHSRP protein, human; D016601:RNA-Binding Proteins; D015534:Trans-Activators