MicroRNA-29 in the adaptive immune system: setting the threshold
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Cellular and Molecular Life Sciences
MULTI-AUTHOR REVIEW
MicroRNA-29 in the adaptive immune system: setting the threshold Adrian Liston • Aikaterini S. Papadopoulou Dina Danso-Abeam • James Dooley
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Received: 8 August 2012 / Revised: 9 August 2012 / Accepted: 9 August 2012 / Published online: 13 September 2012 Ó Springer Basel AG 2012
Abstract Recent research into the role of microRNA (miR) in the immune system has identified the miR-29 family as critical regulators of key processes in adaptive immunity. The miR-29 family consists of four members with shared regulatory capacity, namely miR-29a, miR-29b-1, miR-29b-2 and miR-29c. Being expressed in both T and B cells, as well as the main accessory cell types of thymic epithelium and dendritic cells, the miR-29 family has been identified as a putative regulator of immunity due to the predicted suppression of key immunological pathways. The generation of a series of in vivo molecular tools targeting the miR-29 family has identified the critical role of these miR in setting the molecular threshold for three central events in adaptive immunity: (1) control over thymic production of T cells by modulating the threshold for infection-associated thymic involution, (2) creating a neutral threshold for T cell polarization following activation, and (3) setting the threshold for B cell oncogenic transformation. These results identify the miR-29 family as potent immune modulators which have already been exploited through the evolution of a viral mimic and could potentially be exploited further for therapeutic intervention. Keywords MicroRNA Thymus T cells B cells Immunology Leukemia
A. Liston D. Danso-Abeam J. Dooley (&) Autoimmune Genetics Laboratory, VIB and University of Leuven, Leuven, Belgium e-mail: [email protected] A. S. Papadopoulou Center for Human Genetics, VIB and University of Leuven, Leuven, Belgium
Introduction MicroRNA (miR) are small noncoding RNA with the capacity to interfere in the expression of protein-coding mRNA. The regulation of mRNA by miR has a potent effect on many cellular functions. Within the adaptive immune system, several families of miR have been identified to be of elevated importance, due to functions in regulating key immunological pathways [1]. Recent studies have added the miR-29 family to the list of key miR in the adaptive immune system. The miR-29 family consists of four closely related members, miR-29a, miR-29b-1, miR-29b-2 and miR-29c. Each member is characterized by the same ‘‘seed region’’ (positions two to eight of the 50 end) and hence heavily overlap in their predicted mRNA targeting. There are two bi-cistronic clusters of miR-29, the miR-29a/b-1 cluster and the miR-29b-2/c cluster, which have arisen by gene duplication [2, 3]. The miR-29a/b-1 cluster is located on the antisense strand of chromosome 7 of the human genome and chromosome 6 of the mouse genome, while the miR-29b-2/c cluster is located on the antisense strand of the human genome and the sense strand of the mouse genome, and on chromosome 1
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