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AU-rich RNA binding proteins in hematopoiesis and leukemogenesis

Baou, Maria and Norton, John D. and Murphy, John J. (2011) AU-rich RNA binding proteins in hematopoiesis and leukemogenesis. Blood, 118 (22). pp. 5732-5740. ISSN 0006-4971

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Official URL: http://dx.doi.org/10.1182/blood-2011-07-347237

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.

Item Type:Article
Research Community:University of Westminster > Life Sciences, School of
ID Code:10230
Deposited On:19 Jan 2012 12:19
Last Modified:19 Jan 2012 12:19

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