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* Australian Research Council Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia;
T Cell Laboratory, Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Austin Health, Heidelberg, Victoria, Australia; and
Australian Stem Cell Centre, Melbourne, Australia
Previous research into the molecular mechanisms that underlie Ag-specific CD8+ T cell differentiation and function has largely focused on the role of proteins. However, it is now apparent that the mammalian genome expresses large numbers of long (>200 nt) nonprotein-coding RNAs (ncRNAs), and there is increasing evidence that these RNAs have important regulatory functions, particularly in the regulation of epigenetic processes underpinning cell differentiation. In this study, we show that CD8+ T cells express hundreds of long ncRNAs, many of which are lymphoid-specific and/or change dynamically with lymphocyte differentiation or activation. Numerous ncRNAs surround or overlap immunologically important protein-coding genes and can be predicted to function via a range of regulatory mechanisms. The overlap of many long ncRNAs expressed in CD8+ T cells with microRNAs and small interfering RNAs further suggests that long ncRNAs may be processed into and exert their effects via smaller functional species. Finally, we show that the majority of long ncRNAs expressed in CD8+ T cells harbor signatures of evolutionary conservation, secondary structures, and/or regulated promoters, further supporting their functionality. Taken together, our findings represent the first systematic discovery of long ncRNAs expressed in CD8+ T cells and suggest that many of these transcripts are likely to play a role in adaptive immunity.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by funding from the National Health and Medical Research Council (to K.C.P.), the Wellcome Trust (to W.C.), the Foundation for Research, Science and Technology of New Zealand (to M.E.D.), Australian Postgraduate Award (to T.R.M.), the Australian Research Council, University of Queensland, and the Queensland State Government. (to J.S.M.).
2 Current address: Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge MA 02138.
3 Address correspondence and reprint requests to Dr. John S. Mattick, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072 Australia. E-mail address: j.mattick{at}imb.uq.edu.au
4 Abbreviations used in this paper: ncRNA, nonprotein coding RNA; GNF, Genomics Institute of Novartis Research Foundation; GO, Gene Ontology; ICS, intracellular cytokine staining; miRNA, microRNA; RefSeq, reference sequence; rVV, recombinant vaccinia virus; siRNA, small interfering RNA; UTR, untranslated region.
5 The online version of this article contains supplemental material.
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  M. E. Dinger, P. P. Amaral, T. R. Mercer, and J. S. Mattick Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications Brief Funct Genomic Proteomic, November 1, 2009; 8(6): 407 - 423. [Abstract] [Full Text] [PDF]
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