RESEARCH - SiLEncing SLE: the power and promise of small noncoding RNAs

[Guest guest]

Curr Opin Rheumatol. 2008 Sep;20(5):526-31.

SiLEncing SLE: the power and promise of small noncoding RNAs.

Rigby RJ, Vinuesa CG.

Division of Immunity and Infection, Curtin School of Medical

Research, Australian National University, Canberra, Australia.

PURPOSE OF REVIEW: In this study, we outline the evidence suggesting

that defects in the RNA silencing machinery can lead to the prototypic

systemic autoimmune disease, systemic lupus erythematosus, and

describe the potential for RNA interference to provide novel

therapeutic agents.

RECENT FINDINGS: Over the last year, a class of small noncoding

RNAs--microRNAs--have been shown to play key roles in immune

regulation including T-cell selection in the thymus, B cell affinity

maturation and selection in germinal centres, and development of

regulatory T cells, suggesting that the microRNA machinery may be

crucial in the maintenance of immunological tolerance. Two RNA

silencing mechanisms have been shown to be involved in lupus

pathogenesis: failed Roquin-mediated repression of inducible

costimulatory receptors messenger RNA through miR-101 in

roquin(san/san) mice and decreased expression of pro-apoptotic

molecule and phosphatase and tensin homologue on chromosome 10 in mice

transgenic for the miR-17-92 cluster, leading to lymphoproliferation

and other lupus manisfestations. MicroRNA array experiments performed

on peripheral blood mononuclear cells have revealed different

expression profiles in systemic lupus erythematosus patients. RNA

interference has also been used ex vivo to silence dysregulated T-cell

molecules in cells from systemic lupus erythematosus patients.

SUMMARY: Dysregulation of the RNA silencing machinery has been

implicated in systemic lupus erythematosus pathogenesis. Although

microRNA profiling may prove to be a useful diagnostic and prognostic

tool for a notoriously heterogeneous disease, manipulation of RNA

interference emerges as a powerful and potentially specific means to

correct dysregulated gene expression in systemic lupus erythematosus

patients.

PMID: 18698172

http://www.ncbi.nlm.nih.gov/pubmed/18698172

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Not an MD